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原癌基因 Pim-3 在胰腺癌发生中的作用机制以及分子靶向治疗药物的开发
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原原原原 原原原原 Pim-3 Pim-3 原原原原原原原原原原原原原原原原原 原原原原原原原原原原原原原原原原原 原原原原原原原原 原原原原原原原原 原原原原原原原原原原原原原原原原 原原原原原原原原原原原原原 原 原原
description
原癌基因 Pim-3 在胰腺癌发生中的作用机制以及分子靶向治疗药物的开发. 李 影奕. 复旦大学附属肿瘤医院实验研究中心 复旦大学上海医学院肿瘤学系. 报告内容. Pim-3 激酶在胰腺癌发生中的作用机制 以 Pim-3 为靶向治疗分子的新型有效的 抗肿瘤药物的开发. Pim-3 激酶在胰腺癌发生中的作用机制. 研究背景. Pim 基因敲出的小鼠生命力旺盛且可繁殖后代. Pim-3 与恶性转化相关. Pim-3 是原癌基因。. p34. Pim-1. p40. p37. p34. Pim-2. p34. Pim-3. - PowerPoint PPT Presentation
Transcript of 原癌基因 Pim-3 在胰腺癌发生中的作用机制以及分子靶向治疗药物的开发
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Pim-3
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Pim-3
Pim-3
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Pim-3
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p34p34p34p37p40Kinase DomainPim-1Pim-2Pim-3Deneen B. et al. Mol Cell Biol 2003;23:3897Mikkers H. et al. Mol Cell Biol 2004;24:6104Pim-3 Pim Pim-3
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Pim-3 is a proto-oncogene with serine/threonine kinase activity.Fujii C et al. Int J Cancer. 2005 Mar 20;114(2):209-18. Pim-3
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Normal TissueCancer TissuesPim-3 PCI55PCI35-Pim-3
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Actin3643kDaWCL Pim-3shRNA Non Scramble Pim-3PCI55Pim-3 siRNA Pim-3Scramble shRNAPim-3 shRNADNA ContentNo shRNASubG1Annexin VPim-3 shRNAScramble shRNAPim-3 shRNAScramble shRNA 0 1 2 3 4 5 8 7 6 5 4 3 2 1 0Cell viability ratioTime after passage (days)****
Graph2
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2.65582655832.46877828052.2253122398
4.25943992774.2506787332.6860949209
5.29900632345.19366515843.8084929226
6.40831074986.72669683264.4845961699
6.13098464325.95113122174.5903413822
No-shRNA
Scramble siRNA
Pim3 siRNA
PCI55-1
N0-treatmentScramble siRNAPim3 siRNAN0-treatmentScramble siRNAPim3 siRNA
average0day0.221410.215410.21461STDEV0day0.00634822810.01531796330.008475848
1day0.54262.4507678410.52362.43082636950.39041.81919850891day0.06738545840.08067403550.0385784914
2day0.94544.27009936770.91024.22562674090.64523.00652376512day0.06966204130.11773784440.0718693259
3day1.2625.70009033421.21745.6518105850.91484.26281453873day0.09302419040.10142879280.0777058556
4day1.41866.40740740741.45146.73816155991.07725.01957129544day0.13877247570.12770003920.0719944442
5day1.41846.4065040651.3876.43918291551.10265.13793103455day0.0666843310.06784172760.0909686759
N0-treatmentScramble siRNAPim3 siRNAN0-treatmentScramble siRNAPim3 siRNA
average0day0.221410.22110.24021STDEV0day0.00829457650.01692631090.0159279628
1day0.5882.65582655830.54562.46877828050.44381.62531223981day0.10342871940.11011948060.0661226134
2day0.943044.25943992770.93944.2506787330.53722.68609492092day0.05726738160.06318069330.0637314679
3day1.17325.29900632341.14785.19366515840.8083.80849292263day0.06874009020.07357784990.0449722136
4day1.41886.40831074981.48666.72669683261.0184.48459616994day0.13682178190.10898990780.0672123501
5day1.35746.13098464321.31525.95113122171.04944.59034138225day0.08539496470.08136153880.0775325738
subratio
Scramble siRNAPim3 siRNAScramble siRNAPim3 siRNA
01110111
12.65582655832.46877828052.225312239812.4507678412.43082636952.1891985089
24.25943992774.2506787332.686094920924.27009936774.22562674093.3065237651
35.29900632345.19366515843.808492922635.70009033425.6518105854.2628145387
46.40831074986.72669683264.484596169946.40740740746.73816155995.0195712954
56.13098464325.95113122174.590341382256.4065040656.43918291555.1379310345
PCI55-1
No-shRNA
Scramble siRNA
Pim3 siRNA
Time after passage (days)
Cell proliferation ratio
The Effects of Pim3 siRNA Vector on Proliferation of PCI55 Cells
PCI55
No-shRNA
Scramble siRNA
Pim3 siRNA
Time affter passage (days)
Cell proliferation ratios
PCI35-1
No-shRNA
Scramble siRNA
Pim3 siRNA
PCI35
vector-0-few-radiovector-0-few-sub
450(N)450-655450(SV)450-655450(PV)450-655655450450-655450(SV)450-655450(PV)450-655655
0.2540.2150.2720.2250.2760.2250.0390.0470.0510.2530.2170.2870.240.3150.260.0360.0470.055
0.260.2210.2910.240.2690.2160.0390.0510.0530.2540.2180.2930.2370.3080.2410.0360.0560.067
0.2590.2190.2610.210.2730.220.040.0510.0530.2510.2160.2620.2030.3220.2490.0350.0590.073
0.2730.2320.2510.1970.2550.20.0410.0540.0550.2780.2360.2760.2070.3120.2330.0420.0690.079
0.2610.220.2540.2050.2590.2120.0410.0490.0470.2620.220.2730.2180.2730.2180.0420.0550.055
average0.22140.21540.21460.22140.2210.2402
STDEV0.00634822810.01531796330.0084758480.00829457650.01692631090.0159279628
vector-24-few-radiovector-24-few-sub
450450-655450(SV)450-655450(PV)450-655655450450-655450(SV)450-655450(PV)450-655655
0.6460.5990.6580.60.50.4410.0470.0580.0590.7870.7420.7450.6520.6110.5120.0450.0930.099
0.5980.550.6840.620.4580.3940.0480.0640.0640.640.5950.7390.6530.510.4190.0450.0860.091
0.5910.5440.5480.4910.4140.3570.0470.0570.0570.6580.6110.6560.5570.5290.4240.0470.0990.105
0.6420.590.510.4510.4050.3480.0520.0590.0570.5890.5240.5360.4240.4750.3560.0650.1120.119
0.4760.430.5060.4560.4610.4120.0460.050.0490.520.4680.5060.4420.5670.5080.0520.0640.059
average0.54260.52360.39040.01037347730.5880.54560.4438
STDEV0.06738545840.08067403550.03857849140.10342871940.11011948060.0661226134
vector-48-few-radiovector-48-few-sub
450450-655450(SV)450-655450(PV)450-655655450450-655450(SV)450-655450(PV)450-655655
1.0630.9871.0390.940.8260.7240.0760.0990.1021.05511.00310.9260.8440.7030.6190.0520.0820.084
1.0841.0031.1591.0710.7260.6370.0810.0880.0890.9610.91.0360.9380.670.5660.0610.0980.104
1.0780.9911.0490.950.8050.7070.0870.0990.0981.06411.00411.0690.9770.6470.5560.060.0920.091
0.9990.9030.8990.7780.7360.6090.0960.1210.1270.9830.9251.0921.0120.5510.4730.0580.080.078
0.90.8430.8780.8120.6090.5490.0570.0660.060.9340.8830.9810.9260.5240.4720.0510.0550.052
average0.94540.91020.64520.00263075170.943040.93940.5372
STDEV0.06966204130.11773784440.07186932590.05726738160.06318069330.0637314679
vector-72-few-radiovector-72-few-sub
450450-655450(SV)450-655450(PV)450-655655450450-655450(SV)450-655450(PV)450-655655
1.3751.3371.2981.2471.0320.9770.0380.0510.0551.2641.2251.1951.1480.8350.7870.0390.0470.048
1.3441.3061.31.2481.0390.9810.0380.0520.0581.1081.0681.1711.1210.9320.8810.040.050.051
1.3491.311.3381.2821.0130.9490.0390.0560.0641.2821.2411.2011.1530.8690.820.0410.0480.049
1.2961.2521.3451.2720.9440.8610.0440.0730.0831.1931.1511.1941.1390.8390.7840.0420.0550.055
1.1491.1051.0981.0380.8690.8060.0440.060.0631.2221.1811.2281.1780.8180.7680.0410.050.05
average1.2621.21740.91480.0007322811.17321.14780.808
STDEV0.09302419040.10142879280.07770585560.06874009020.02082546520.0449722136
vector-96-few-radiovector-96-few-sub
450450-655450(SV)450-655450(PV)450-655655450450-655450(SV)450-655450(PV)450-655655
1.451.41.3321.261.2731.1960.050.0720.0771.531.4731.4681.3821.0020.9120.0570.0860.09
1.5861.5341.5071.431.171.0870.0520.0770.0831.6541.5731.5811.4861.1021.0040.0810.0950.098
1.4181.3651.5641.4851.111.0290.0530.0790.0811.4931.4051.6321.5281.1441.040.0880.1040.104
1.5041.4481.6921.6151.1331.0590.0560.0770.0741.2931.2011.591.4821.1991.0930.0920.1080.106
1.3971.3461.5241.4671.0681.0150.0510.0570.0531.5221.4421.6641.5551.1451.0410.080.1090.104
average1.41861.45141.07721.41881.48661.018
STDEV0.07528479260.12770003920.07199444420.13682178190.06586956810.0672123501
vector-120-few-radiovector-120-few-sub
450450-655450(SV)450-655450(PV)450-655655450450-655450(SV)450-655450(PV)450-655655
1.591.4991.5371.4331.2151.1210.0880.0930.0941.5151.4241.4211.3171.1481.0420.0910.1040.106
1.51.4251.5341.451.3331.2340.0960.0980.0991.4841.4091.51.4161.2681.180.0750.0840.088
1.5391.4551.4951.3891.1841.0760.1050.110.1081.5031.4191.4531.3471.1351.0270.0840.1060.108
1.4641.391.491.3871.0890.9810.1080.1080.1081.3741.31.4071.3041.0790.9730.0740.1030.106
1.3811.3231.3391.2761.211.1010.0760.1090.1091.2931.2351.2551.1921.0831.0250.0580.0630.058
average1.41841.3871.10261.35741.31521.0494
STDEV0.0666843310.06784172760.09096867590.08539496470.08136153880.0775325738
N0-treatmentScramble siRNAPim3 siRNAN0-treatmentScramble siRNAPim3 siRNA
average0day0.257210.240810.2491STDEV0day0.00634822810.01531796330.008475848
1day0.6962.70606531880.67962.82225913620.63782.56144578311day0.06738545840.08067403550.0385784914
2day1.03984.04276827370.9964.13621262460.7883.16465863452day0.06966204130.11773784440.0718693259
3day1.35125.25349922241.30745.42940199340.95023.8160642573day0.09302419040.10142879280.0777058556
4day1.64386.39113530331.43685.96677740861.01964.09477911654day0.13877247570.12770003920.0719944442
5day1.59346.19517884911.32045.48338870430.84243.38313253015day0.0666843310.06784172760.0909686759
N0-treatmentScramble siRNAPim3 siRNAN0-treatmentScramble siRNAPim3 siRNA
average0day0.25410.233210.24861STDEV0day0.00829457650.01692631090.0159279628
1day0.71442.81259842520.6892.95454545450.51242.06114239741day0.10342871940.11011948060.0661226134
2day1.05624.15826771651.08524.6535162950.77483.11665325822day0.05726738160.06318069330.0637314679
3day1.33945.27322834651.35845.82504288160.9153.6806114243day0.06874009020.07357784990.0449722136
4day1.75066.89212598431.57326.74614065180.994444day0.13682178190.10898990780.0672123501
5day1.66186.5425196851.36185.83962264150.77763.12791633155day0.08539496470.08136153880.0775325738
subratio
N0-treatmentScramble siRNAPim3 siRNAN0-treatmentScramble siRNAPim3 siRNA
0111.040111
12.81259842522.95454545452.061142397412.70606531882.82225913622.5614457831
24.15826771654.6535162953.116653258224.04276827374.13621262463.1646586345
35.27322834655.82504288163.68061142435.25349922245.42940199343.816064257
46.89212598436.7461406518446.39113530335.96677740864.0947791165
56.5425196855.83962264153.127916331556.19517884915.48338870433.3831325301
N0-treatment
Scramble siRNA
Pim3 siRNA
Time after passage (Days)
Cell Proliferation Ratios
The Effects of Pim-3 siRNA Vector on Proliferation of PCI35 Cells
N0-treatment
Scramble siRNA
Pim3 siRNA
vector-0-more-ratiovector-0-more-sub
450(N)450-655450(SV)450-655450(PV)450-655655450(N)450-655450(SV)450-655450(PV)450-655655
0.2560.2180.3090.2550.2860.2270.0380.0540.0590.2780.2440.3180.2460.3080.2270.0340.0720.081
0.2960.2590.2360.1830.3320.2720.0370.0530.060.2950.260.2460.1680.3330.2460.0350.0780.087
0.3080.2680.330.2630.3180.250.040.0670.0680.3120.2760.350.2610.3460.2510.0360.0890.095
0.3080.2650.3160.2420.3370.2650.0430.0740.0720.2650.2250.350.2490.3880.2820.040.1010.106
0.3190.2760.3180.2610.2820.2310.0430.0570.0510.3060.2650.3160.2420.3030.2370.0410.0740.066
average0.25720.24080.2490.64959880510.2540.23320.2486
STDEV0.02275302180.03333466660.01996246480.01988718180.03713084970.0207918253
vector-24-more-radiovector-24-more-sub
450(N)450-655450(SV)450-655450(PV)450-655655450(N)450-655450(SV)450-655450(PV)450-655655
0.7750.720.8020.7160.7010.6080.0550.0860.0930.7320.6840.8050.7420.6190.5530.0480.0630.066
0.8530.7940.8170.7290.7230.6280.0590.0880.0950.8850.8360.7690.6960.6180.5390.0490.0730.079
0.7590.6830.7830.6730.6440.530.0760.110.1140.7830.7330.8640.7940.5160.4480.050.070.068
0.7510.6740.790.6820.7150.6040.0770.1080.1110.7950.7420.70.630.6020.5370.0530.070.065
0.6620.6090.6580.5980.5750.5190.0530.060.0560.6270.5770.6360.5830.5350.4850.050.0530.05
average0.6960.67960.57780.00479555550.71440.6890.5124
STDEV0.06782698580.05116932670.04965078050.09446851330.08455767260.0443260646
vector-48-more-radiovector-48-more-sub
450(N)450-655450(SV)450-655450(PV)450-655655450(N)450-655450(SV)450-655450(PV)450-655655
1.311.2271.221.1030.7880.670.0830.1170.1181.2781.231.21.1370.8190.7530.0480.0630.066
0.9670.8871.060.9540.7590.6510.080.1060.1080.9760.9271.0270.9540.7490.670.0490.0730.079
1.010.9371.0610.9440.820.7020.0730.1170.1181.0070.9571.1341.0640.9280.860.050.070.068
1.1431.0811.21.1020.6980.6020.0620.0980.0961.3021.2491.3261.2560.8640.7990.0530.070.065
1.1171.0670.9360.8770.7220.6650.050.0590.0570.9680.9181.0681.0150.8420.7920.050.0530.05
average1.03980.9960.6581.05621.08520.7748
STDEV0.13360089820.10162922810.03644859390.1680853950.11666919040.0699978571
vector-72-more-radiovector-72-more-sub
450(N)450-655450(SV)450-655450(PV)450-655655450(N)450-655450(SV)450-655450(PV)450-655655
1.3741.3331.1581.1021.0631.0110.0410.0560.0521.3751.3371.3131.2461.0360.9640.0380.0670.072
1.3631.3211.371.3080.9030.8490.0420.0620.0541.3361.2981.3811.3040.8910.8140.0380.0770.077
1.3171.2741.3821.331.0891.0390.0430.0520.051.321.2791.4291.3611.0951.0190.0410.0680.076
1.341.2941.361.3020.8670.8120.0460.0580.0551.3651.321.3791.2960.8480.7570.0450.0830.091
1.5781.5341.5441.4951.0881.040.0440.0490.0481.5071.4631.6451.5851.0781.0210.0440.060.057
average1.35121.30740.95021.33941.35840.915
STDEV0.10475065630.13957363650.11066480920.0724934480.13308005110.1220839875
vector-96-mor-radiovector-96-more-sub
450(N)450-655450(SV)450-655450(PV)450-655655450(N)450-655450(SV)450-655450(PV)450-655655
1.6641.6111.6451.5571.1471.0530.0530.0880.0941.7181.6341.6241.5171.1611.0510.0840.1070.11
1.6361.5861.6281.5381.2961.1990.050.090.0971.671.5821.7181.6141.2541.1470.0880.1040.107
1.8531.7961.5151.4211.2371.1380.0570.0940.0992.031.9351.6941.581.221.1050.0950.1140.115
1.7251.6651.371.2860.910.8230.060.0840.0871.8861.7951.5461.4360.9190.8050.0910.110.114
1.6131.5611.4421.3820.940.8850.0520.060.0551.8761.8071.8261.7190.9690.8640.0690.1070.105
average1.64381.43681.01961.75061.57320.9944
STDEV0.09339004230.11256420390.16131273970.1424580640.10600801860.1513267987
vector-120-mor-radiovector-120-more-sub
450(N)450-655450(SV)450-655450(PV)450-655655450(N)450-655450(SV)450-655450(PV)450-655655
1.8341.751.7221.6180.9380.8440.0840.1040.0941.8211.7151.7831.6570.9370.8230.1060.1260.114
1.7461.6611.6671.5640.9640.8720.0850.1030.0921.8171.7111.6731.5460.9540.840.1060.1270.114
1.5861.4991.2691.171.0870.9890.0870.0990.0981.6511.5351.3141.1910.9550.8360.1160.1230.119
1.7121.6281.3071.1870.8860.7630.0840.120.1231.6971.591.3541.2390.8360.7230.1070.1150.113
1.4871.4291.1321.0630.8080.7440.0580.0690.0641.8461.7581.3031.1760.7950.6660.0880.1270.129
average1.59341.32040.84241.66181.36180.7776
STDEV0.12867517240.25227821940.09792497130.0945235420.22352113990.0787419837
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Pim-1, Pim-2BadSer136 Survival FactorPI3KAKTBadSer112Pim-1 and Pim-2 Can Inactiavte Pro-apoptotic Molecule, Bad, by Phosphorylating Its Serine ResiduesBadBcl-XL+Bcl-XL
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Pim-3BadPim-3/BadPCI55 Pim-3 Bad a-Pim3HeLaa-Bada-IgGIP: PCI35 PCI55 PCI552526kDaBadIgGBlot: anti-Pim3Blot: anti-Bad5036Pim-3IgGImmunoprecipitation with anti-Pim-3 Western blotting with anti-Bad Washing with Stripping bufferWestern blotting with anti-Pim-3
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Pim-3pBad112Pim-3/pBad112PCI35 PCI5520mmPim-3Bad
-
ActinBadpBad112pBad136pBad155 Pim-32626262643KDa36shRNA Non Scramble Pim-3PCI55Pim-3 Bad112
-
1Pim-3
-
Pim-3
-
55%Pim-3
-
Pim-3Pim-170%Pim-3-Pim-3DrugBankPubChem23 Pim-3-stemonamide
-
T-10 >T-6, T-10 >T-4 >T-5, T-10 >T-2 >T-3
-
Pim-3Pim-1Pim-2T2, T5Pim
Chart4
100100100
101098.7639286367
91.378184193361.896.6327711137
79.229261920359.293.9536016562
55.649902024833.389.3259453206
18.354016982410.880.9839858735
11178
T-2
T-5
T-10
Small molecule compound (M)
% Pim-1 activity
kawakami
Pim-1Pim-1
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
10
2091.378184193393.609022556461.869.92091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
320111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637682065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
kawakami
100100100100
10101010
91.378184193393.609022556461.869.9
79.229261920380.236305048359.264.6
55.649902024863.963480128933.366.6
18.354016982438.936627282510.814.2
111512
T-2
T-18
T-5
No.5
Small molecule compound (M)
% Pim-1 activity
Pim-1,-2,-T2,T5,T10
100100100100
10101097.7225672878
65.288667141855.422343324371.787296898185.5072463768
42.551674982240.217983651257.902511078390.3726708075
23.307198859621.035422343345.347119645582.0910973085
9.764789736310.13623978213.2939438710.5590062112
0.30.051.22
T-2
T-18
T-5
No.5
Small molecule compound (M)
% Pim-2 activity
Li-T2,T5,T10
100100100100100
10101079.310
90.20363236186.3657693992202020
31.2531.2531.2531.2590.2
72.702256466770.487736109586.961.740
62.562.562.562.588.1
51.62355531136.975573682463.449.680
12512512512583.8
11.55751238321.17071105321.312.2160
25025025025075.3
8.1452944414210320320
50050050050065.6
100010001000100039.8
T-2
T-18
T-5
No.5
T-10
Small molecule compound (M)
% Pim-3 activity
Li-T2,T5,T18,T10
79.3
90.20363236186.3657693992202020
31.2531.2531.2531.2590.2
72.702256466770.487736109586.961.740
62.562.562.562.588.1
51.62355531136.975573682463.449.680
12512512512583.8
11.55751238321.17071105321.312.2160
25025025025075.3
8.1452944414210320320
50050050050065.6
100010001000100039.8
T-2
T-18
T-5
No.5
T-10
Sheet2
65.288667141855.422343324371.787296898185.5072463768
42.551674982240.217983651257.902511078390.3726708075
23.307198859621.035422343345.347119645582.0910973085
9.764789736310.13623978213.2939438710.5590062112
0.30.051.22
1000100010001000
T-2
T-18
T-5
No.5
Li-1
91.378184193393.609022556461.869.9
79.229261920380.236305048359.264.6
55.649902024863.963480128933.366.6
18.354016982438.936627282510.814.2
111512
1000100010001000
T-2
T-18
T-5
No.5
Pim-1Pim-1
T-2T-5T-10Pim-1
0100100100T-2T-18T-5No.5
4099.494611216
8091.378184193361.898.7639286367
16079.229261920359.296.6327711137
32055.649902024833.393.9536016562
64018.354016982410.889.32594532062091.378184193393.609022556461.869.9
128011180.9839858735
200010.3784079.229261920380.236305048359.264.6
Pim-28055.649902024863.963480128933.366.6
T-2T-5T-1016018.354016982438.936627282510.814.2
0100100100
4099.3021148036320111512
8065.288667141871.787296898199.2950654582
16042.551674982257.902511078398.28801611281000
32023.307198859645.347119645591.1379657603
6409.764789736313.2939438793.0513595166
12802488.5196374622Pim-2
20000.10.588.5Pim-2
T-2T-18T-5No.5
2065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.5590062112
3200.30.051.22
1000
T-2T-5T-10
0100100100Pim-3
8078.774.1
62.590.2T-2T-18T-5No.5T-10
16086.971.7Pim-3
25088.1
32063.452.879.3
60083.82090.20363236186.3657693992
64021.343.531.2590.2
8004072.702256466770.487736109586.961.7
100075.362.588.1
12805.010.08051.62355531136.975573682463.449.6
200065.612583.8
16011.55751238321.17071105321.312.2
400039.825075.3
3208.1452944414210.0
50065.6
100039.8
T-2
T-5
T-10
T-2
T-5
T-10
100100100
78.774.180
62.562.590.2
86.971.7160
25025088.1
63.452.8320
60060083.8
21.343.5640
800800800
1000100075.3
5101280
2000200065.6
4000400039.8
T-2
T-5
T-10
Pim-1Pim-1
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
10
2091.378184193393.609022556461.869.92091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
320111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637682065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
90.20363236186.36576939922020
31.2531.2531.2590.2
72.702256466770.487736109586.940
62.562.562.588.1
51.62355531136.975573682463.480
12512512583.8
11.55751238321.17071105321.3160
25025025075.3
8.1452944414210320
50050050065.6
10001000100039.8
T-2
T-18
T-5
T-10
65.288667141855.422343324371.7872968981
42.551674982240.217983651257.9025110783
23.307198859621.035422343345.3471196455
9.764789736310.13623978213.29394387
0.30.051.2
100010001000
T-2
T-18
T-5
91.378184193393.609022556461.8
79.229261920380.236305048359.2
55.649902024863.963480128933.3
18.354016982438.936627282510.8
11151
100010001000
T-2
T-18
T-5
100100
1010
91.378184193361.8
79.229261920359.2
55.649902024833.3
18.354016982410.8
111
T-2
T-5
100100
1010
65.288667141871.7872968981
42.551674982257.9025110783
23.307198859645.3471196455
9.764789736313.29394387
0.31.2
T-2
T-5
100100100
101010
90.2036323612020
31.2531.2590.2
72.702256466786.940
62.562.588.1
51.62355531163.480
12512583.8
11.55751238321.3160
25025075.3
8.145294441410320
50050065.6
1000100039.8
T-2
T-5
T-10
100100
1010
91.378184193361.8
79.229261920359.2
55.649902024833.3
18.354016982410.8
111
T-2
T-5
100100
1010
65.288667141871.7872968981
42.551674982257.9025110783
23.307198859645.3471196455
9.764789736313.29394387
0.31.2
T-2
T-5
Pim-1Pim-1
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
10
2091.378184193393.609022556461.869.92091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
320111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637682065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
100100100100
10101010
90.20363236186.36576939922020
31.2531.2531.2590.2
72.702256466770.487736109586.940
62.562.562.588.1
51.62355531136.975573682463.480
12512512583.8
11.55751238321.17071105321.3160
25025025075.3
8.1452944414210320
50050050065.6
10001000100039.8
T-2
T-18
T-5
T-10
90.20363236186.36576939922020
31.2531.2531.2590.2
72.702256466770.487736109586.940
62.562.562.588.1
51.62355531136.975573682463.480
12512512583.8
11.55751238321.17071105321.3160
25025025075.3
8.1452944414210320
50050050065.6
10001000100039.8
T-2
T-18
T-5
T-10
65.288667141855.422343324371.7872968981
42.551674982240.217983651257.9025110783
23.307198859621.035422343345.3471196455
9.764789736310.13623978213.29394387
0.30.051.2
100010001000
T-2
T-18
T-5
91.378184193393.609022556461.8
79.229261920380.236305048359.2
55.649902024863.963480128933.3
18.354016982438.936627282510.8
11151
100010001000
T-2
T-18
T-5
100100100
101010
91.378184193393.609022556461.8
79.229261920380.236305048359.2
55.649902024863.963480128933.3
18.354016982438.936627282510.8
11151
T-2
T-18
T-5
100100100
101010
65.288667141855.422343324371.7872968981
42.551674982240.217983651257.9025110783
23.307198859621.035422343345.3471196455
9.764789736310.13623978213.29394387
0.30.051.2
T-2
T-18
T-5
Pim-1Pim-1
T-2T-18T-5No.50um100T-2T-18T-5No.5
01001001001000.4um
0.8um91.3781841933
0.41.6um79.2292619203
3.2um55.6499020248
0.891.378184193393.609022556461.869.96.4um18.35401698242091.378184193393.609022556461.869.9
12.8um11
1.679.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
3.255.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
6.418.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
12.8111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637681.51511035652065.288667141855.422343324371.787296898185.5072463768
4.5499232129
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
Pim-1Pim-1
T-2T-18T-5No.5T-10T-2T-18T-5No.5
0100100100100100
1098.7639286367
2091.378184193393.609022556461.869.996.63277111372091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.693.95360165624079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.689.32594532068055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.280.983985873516018.354016982438.936627282510.814.2
32011151278320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-10T-2T-18T-5No.5
0100100100100100
1097.722567287899.3021148036
2065.288667141855.422343324371.787296898185.507246376898.28801611282065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.372670807591.13796576034042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.091097308593.05135951668023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.559006211288.51963746221609.764789736310.13623978213.2939438710.5590062112
3200.30.051.2288.53200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
T-2
T-5
T-10
Small molecule compound (M)
% Pim-1 activity
T-2
T-5
T-10
Small molecule compound (M)
% Pim-2 activity
100100100
101010
90.2036323612020
31.2531.2590.2
72.702256466786.940
62.562.588.1
51.62355531163.480
12512583.8
11.55751238321.3160
25025075.3
8.145294441410320
50050065.6
1000100039.8
T-2
T-5
T-10
Small molecule compound (M)
% Pim-3 activity
79.3
90.20363236186.3657693992202020
31.2531.2531.2531.2590.2
72.702256466770.487736109586.961.740
62.562.562.562.588.1
51.62355531136.975573682463.449.680
12512512512583.8
11.55751238321.17071105321.312.2160
25025025025075.3
8.1452944414210320320
50050050050065.6
100010001000100039.8
T-2
T-18
T-5
No.5
T-10
65.288667141855.422343324371.787296898185.5072463768
42.551674982240.217983651257.902511078390.3726708075
23.307198859621.035422343345.347119645582.0910973085
9.764789736310.13623978213.2939438710.5590062112
0.30.051.22
1000100010001000
T-2
T-18
T-5
No.5
91.378184193393.609022556461.869.9
79.229261920380.236305048359.264.6
55.649902024863.963480128933.366.6
18.354016982438.936627282510.814.2
111512
1000100010001000
T-2
T-18
T-5
No.5
Chart5
100100100
101099.3021148036
65.288667141871.787296898198.2880161128
42.551674982257.902511078391.1379657603
23.307198859645.347119645593.0513595166
9.764789736313.2939438788.5196374622
0.31.288.5
T-2
T-5
T-10
Small molecule compound (M)
% Pim-2 activity
kawakami
Pim-1Pim-1
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
10
2091.378184193393.609022556461.869.92091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
320111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637682065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
kawakami
100100100100
10101010
91.378184193393.609022556461.869.9
79.229261920380.236305048359.264.6
55.649902024863.963480128933.366.6
18.354016982438.936627282510.814.2
111512
T-2
T-18
T-5
No.5
Small molecule compound (M)
% Pim-1 activity
Pim-1,-2,-T2,T5,T10
100100100100
10101097.7225672878
65.288667141855.422343324371.787296898185.5072463768
42.551674982240.217983651257.902511078390.3726708075
23.307198859621.035422343345.347119645582.0910973085
9.764789736310.13623978213.2939438710.5590062112
0.30.051.22
T-2
T-18
T-5
No.5
Small molecule compound (M)
% Pim-2 activity
Li-T2,T5,T10
100100100100100
10101079.310
90.20363236186.3657693992202020
31.2531.2531.2531.2590.2
72.702256466770.487736109586.961.740
62.562.562.562.588.1
51.62355531136.975573682463.449.680
12512512512583.8
11.55751238321.17071105321.312.2160
25025025025075.3
8.1452944414210320320
50050050050065.6
100010001000100039.8
T-2
T-18
T-5
No.5
T-10
Small molecule compound (M)
% Pim-3 activity
Li-T2,T5,T18,T10
79.3
90.20363236186.3657693992202020
31.2531.2531.2531.2590.2
72.702256466770.487736109586.961.740
62.562.562.562.588.1
51.62355531136.975573682463.449.680
12512512512583.8
11.55751238321.17071105321.312.2160
25025025025075.3
8.1452944414210320320
50050050050065.6
100010001000100039.8
T-2
T-18
T-5
No.5
T-10
Sheet2
65.288667141855.422343324371.787296898185.5072463768
42.551674982240.217983651257.902511078390.3726708075
23.307198859621.035422343345.347119645582.0910973085
9.764789736310.13623978213.2939438710.5590062112
0.30.051.22
1000100010001000
T-2
T-18
T-5
No.5
Li-1
91.378184193393.609022556461.869.9
79.229261920380.236305048359.264.6
55.649902024863.963480128933.366.6
18.354016982438.936627282510.814.2
111512
1000100010001000
T-2
T-18
T-5
No.5
Pim-1Pim-1
T-2T-5T-10Pim-1
0100100100T-2T-18T-5No.5
4099.494611216
8091.378184193361.898.7639286367
16079.229261920359.296.6327711137
32055.649902024833.393.9536016562
64018.354016982410.889.32594532062091.378184193393.609022556461.869.9
128011180.9839858735
200010.3784079.229261920380.236305048359.264.6
Pim-28055.649902024863.963480128933.366.6
T-2T-5T-1016018.354016982438.936627282510.814.2
0100100100
4099.3021148036320111512
8065.288667141871.787296898199.2950654582
16042.551674982257.902511078398.28801611281000
32023.307198859645.347119645591.1379657603
6409.764789736313.2939438793.0513595166
12802488.5196374622Pim-2
20000.10.588.5Pim-2
T-2T-18T-5No.5
2065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.5590062112
3200.30.051.22
1000
T-2T-5T-10
0100100100Pim-3
8078.774.1
62.590.2T-2T-18T-5No.5T-10
16086.971.7Pim-3
25088.1
32063.452.879.3
60083.82090.20363236186.3657693992
64021.343.531.2590.2
8004072.702256466770.487736109586.961.7
100075.362.588.1
12805.010.08051.62355531136.975573682463.449.6
200065.612583.8
16011.55751238321.17071105321.312.2
400039.825075.3
3208.1452944414210.0
50065.6
100039.8
T-2
T-5
T-10
T-2
T-5
T-10
100100100
78.774.180
62.562.590.2
86.971.7160
25025088.1
63.452.8320
60060083.8
21.343.5640
800800800
1000100075.3
5101280
2000200065.6
4000400039.8
T-2
T-5
T-10
Pim-1Pim-1
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
10
2091.378184193393.609022556461.869.92091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
320111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637682065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
90.20363236186.36576939922020
31.2531.2531.2590.2
72.702256466770.487736109586.940
62.562.562.588.1
51.62355531136.975573682463.480
12512512583.8
11.55751238321.17071105321.3160
25025025075.3
8.1452944414210320
50050050065.6
10001000100039.8
T-2
T-18
T-5
T-10
65.288667141855.422343324371.7872968981
42.551674982240.217983651257.9025110783
23.307198859621.035422343345.3471196455
9.764789736310.13623978213.29394387
0.30.051.2
100010001000
T-2
T-18
T-5
91.378184193393.609022556461.8
79.229261920380.236305048359.2
55.649902024863.963480128933.3
18.354016982438.936627282510.8
11151
100010001000
T-2
T-18
T-5
100100
1010
91.378184193361.8
79.229261920359.2
55.649902024833.3
18.354016982410.8
111
T-2
T-5
100100
1010
65.288667141871.7872968981
42.551674982257.9025110783
23.307198859645.3471196455
9.764789736313.29394387
0.31.2
T-2
T-5
100100100
101010
90.2036323612020
31.2531.2590.2
72.702256466786.940
62.562.588.1
51.62355531163.480
12512583.8
11.55751238321.3160
25025075.3
8.145294441410320
50050065.6
1000100039.8
T-2
T-5
T-10
100100
1010
91.378184193361.8
79.229261920359.2
55.649902024833.3
18.354016982410.8
111
T-2
T-5
100100
1010
65.288667141871.7872968981
42.551674982257.9025110783
23.307198859645.3471196455
9.764789736313.29394387
0.31.2
T-2
T-5
Pim-1Pim-1
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
10
2091.378184193393.609022556461.869.92091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
320111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637682065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
100100100100
10101010
90.20363236186.36576939922020
31.2531.2531.2590.2
72.702256466770.487736109586.940
62.562.562.588.1
51.62355531136.975573682463.480
12512512583.8
11.55751238321.17071105321.3160
25025025075.3
8.1452944414210320
50050050065.6
10001000100039.8
T-2
T-18
T-5
T-10
90.20363236186.36576939922020
31.2531.2531.2590.2
72.702256466770.487736109586.940
62.562.562.588.1
51.62355531136.975573682463.480
12512512583.8
11.55751238321.17071105321.3160
25025025075.3
8.1452944414210320
50050050065.6
10001000100039.8
T-2
T-18
T-5
T-10
65.288667141855.422343324371.7872968981
42.551674982240.217983651257.9025110783
23.307198859621.035422343345.3471196455
9.764789736310.13623978213.29394387
0.30.051.2
100010001000
T-2
T-18
T-5
91.378184193393.609022556461.8
79.229261920380.236305048359.2
55.649902024863.963480128933.3
18.354016982438.936627282510.8
11151
100010001000
T-2
T-18
T-5
100100100
101010
91.378184193393.609022556461.8
79.229261920380.236305048359.2
55.649902024863.963480128933.3
18.354016982438.936627282510.8
11151
T-2
T-18
T-5
100100100
101010
65.288667141855.422343324371.7872968981
42.551674982240.217983651257.9025110783
23.307198859621.035422343345.3471196455
9.764789736310.13623978213.29394387
0.30.051.2
T-2
T-18
T-5
Pim-1Pim-1
T-2T-18T-5No.50um100T-2T-18T-5No.5
01001001001000.4um
0.8um91.3781841933
0.41.6um79.2292619203
3.2um55.6499020248
0.891.378184193393.609022556461.869.96.4um18.35401698242091.378184193393.609022556461.869.9
12.8um11
1.679.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
3.255.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
6.418.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
12.8111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637681.51511035652065.288667141855.422343324371.787296898185.5072463768
4.5499232129
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
Pim-1Pim-1
T-2T-18T-5No.5T-10T-2T-18T-5No.5
0100100100100100
1098.7639286367
2091.378184193393.609022556461.869.996.63277111372091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.693.95360165624079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.689.32594532068055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.280.983985873516018.354016982438.936627282510.814.2
32011151278320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-10T-2T-18T-5No.5
0100100100100100
1097.722567287899.3021148036
2065.288667141855.422343324371.787296898185.507246376898.28801611282065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.372670807591.13796576034042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.091097308593.05135951668023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.559006211288.51963746221609.764789736310.13623978213.2939438710.5590062112
3200.30.051.2288.53200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
T-2
T-5
T-10
Small molecule compound (M)
% Pim-1 activity
T-2
T-5
T-10
Small molecule compound (M)
% Pim-2 activity
100100100
101010
90.2036323612020
31.2531.2590.2
72.702256466786.940
62.562.588.1
51.62355531163.480
12512583.8
11.55751238321.3160
25025075.3
8.145294441410320
50050065.6
1000100039.8
T-2
T-5
T-10
Small molecule compound (M)
% Pim-3 activity
79.3
90.20363236186.3657693992202020
31.2531.2531.2531.2590.2
72.702256466770.487736109586.961.740
62.562.562.562.588.1
51.62355531136.975573682463.449.680
12512512512583.8
11.55751238321.17071105321.312.2160
25025025025075.3
8.1452944414210320320
50050050050065.6
100010001000100039.8
T-2
T-18
T-5
No.5
T-10
65.288667141855.422343324371.787296898185.5072463768
42.551674982240.217983651257.902511078390.3726708075
23.307198859621.035422343345.347119645582.0910973085
9.764789736310.13623978213.2939438710.5590062112
0.30.051.22
1000100010001000
T-2
T-18
T-5
No.5
91.378184193393.609022556461.869.9
79.229261920380.236305048359.264.6
55.649902024863.963480128933.366.6
18.354016982438.936627282510.814.2
111512
1000100010001000
T-2
T-18
T-5
No.5
Chart6
100100100
101010
90.2036323612020
31.2531.2590.2
72.702256466786.940
62.562.588.1
51.62355531163.480
12512583.8
11.55751238321.3160
25025075.3
8.145294441410320
50050065.6
1000100039.8
T-2
T-5
T-10
Small molecule compound (M)
% Pim-3 activity
kawakami
Pim-1Pim-1
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
10
2091.378184193393.609022556461.869.92091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
320111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637682065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
kawakami
100100100100
10101010
91.378184193393.609022556461.869.9
79.229261920380.236305048359.264.6
55.649902024863.963480128933.366.6
18.354016982438.936627282510.814.2
111512
T-2
T-18
T-5
No.5
Small molecule compound (M)
% Pim-1 activity
Pim-1,-2,-T2,T5,T10
100100100100
10101097.7225672878
65.288667141855.422343324371.787296898185.5072463768
42.551674982240.217983651257.902511078390.3726708075
23.307198859621.035422343345.347119645582.0910973085
9.764789736310.13623978213.2939438710.5590062112
0.30.051.22
T-2
T-18
T-5
No.5
Small molecule compound (M)
% Pim-2 activity
Li-T2,T5,T10
100100100100100
10101079.310
90.20363236186.3657693992202020
31.2531.2531.2531.2590.2
72.702256466770.487736109586.961.740
62.562.562.562.588.1
51.62355531136.975573682463.449.680
12512512512583.8
11.55751238321.17071105321.312.2160
25025025025075.3
8.1452944414210320320
50050050050065.6
100010001000100039.8
T-2
T-18
T-5
No.5
T-10
Small molecule compound (M)
% Pim-3 activity
Li-T2,T5,T18,T10
79.3
90.20363236186.3657693992202020
31.2531.2531.2531.2590.2
72.702256466770.487736109586.961.740
62.562.562.562.588.1
51.62355531136.975573682463.449.680
12512512512583.8
11.55751238321.17071105321.312.2160
25025025025075.3
8.1452944414210320320
50050050050065.6
100010001000100039.8
T-2
T-18
T-5
No.5
T-10
Sheet2
65.288667141855.422343324371.787296898185.5072463768
42.551674982240.217983651257.902511078390.3726708075
23.307198859621.035422343345.347119645582.0910973085
9.764789736310.13623978213.2939438710.5590062112
0.30.051.22
1000100010001000
T-2
T-18
T-5
No.5
Li-1
91.378184193393.609022556461.869.9
79.229261920380.236305048359.264.6
55.649902024863.963480128933.366.6
18.354016982438.936627282510.814.2
111512
1000100010001000
T-2
T-18
T-5
No.5
Pim-1Pim-1
T-2T-5T-10Pim-1
0100100100T-2T-18T-5No.5
4099.494611216
8091.378184193361.898.7639286367
16079.229261920359.296.6327711137
32055.649902024833.393.9536016562
64018.354016982410.889.32594532062091.378184193393.609022556461.869.9
128011180.9839858735
200010.3784079.229261920380.236305048359.264.6
Pim-28055.649902024863.963480128933.366.6
T-2T-5T-1016018.354016982438.936627282510.814.2
0100100100
4099.3021148036320111512
8065.288667141871.787296898199.2950654582
16042.551674982257.902511078398.28801611281000
32023.307198859645.347119645591.1379657603
6409.764789736313.2939438793.0513595166
12802488.5196374622Pim-2
20000.10.588.5Pim-2
T-2T-18T-5No.5
2065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.5590062112
3200.30.051.22
1000
T-2T-5T-10
0100100100Pim-3
8078.774.1
62.590.2T-2T-18T-5No.5T-10
16086.971.7Pim-3
25088.1
32063.452.879.3
60083.82090.20363236186.3657693992
64021.343.531.2590.2
8004072.702256466770.487736109586.961.7
100075.362.588.1
12805.010.08051.62355531136.975573682463.449.6
200065.612583.8
16011.55751238321.17071105321.312.2
400039.825075.3
3208.1452944414210.0
50065.6
100039.8
T-2
T-5
T-10
T-2
T-5
T-10
100100100
78.774.180
62.562.590.2
86.971.7160
25025088.1
63.452.8320
60060083.8
21.343.5640
800800800
1000100075.3
5101280
2000200065.6
4000400039.8
T-2
T-5
T-10
Pim-1Pim-1
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
10
2091.378184193393.609022556461.869.92091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
320111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637682065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
90.20363236186.36576939922020
31.2531.2531.2590.2
72.702256466770.487736109586.940
62.562.562.588.1
51.62355531136.975573682463.480
12512512583.8
11.55751238321.17071105321.3160
25025025075.3
8.1452944414210320
50050050065.6
10001000100039.8
T-2
T-18
T-5
T-10
65.288667141855.422343324371.7872968981
42.551674982240.217983651257.9025110783
23.307198859621.035422343345.3471196455
9.764789736310.13623978213.29394387
0.30.051.2
100010001000
T-2
T-18
T-5
91.378184193393.609022556461.8
79.229261920380.236305048359.2
55.649902024863.963480128933.3
18.354016982438.936627282510.8
11151
100010001000
T-2
T-18
T-5
100100
1010
91.378184193361.8
79.229261920359.2
55.649902024833.3
18.354016982410.8
111
T-2
T-5
100100
1010
65.288667141871.7872968981
42.551674982257.9025110783
23.307198859645.3471196455
9.764789736313.29394387
0.31.2
T-2
T-5
100100100
101010
90.2036323612020
31.2531.2590.2
72.702256466786.940
62.562.588.1
51.62355531163.480
12512583.8
11.55751238321.3160
25025075.3
8.145294441410320
50050065.6
1000100039.8
T-2
T-5
T-10
100100
1010
91.378184193361.8
79.229261920359.2
55.649902024833.3
18.354016982410.8
111
T-2
T-5
100100
1010
65.288667141871.7872968981
42.551674982257.9025110783
23.307198859645.3471196455
9.764789736313.29394387
0.31.2
T-2
T-5
Pim-1Pim-1
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
10
2091.378184193393.609022556461.869.92091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
320111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637682065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
100100100100
10101010
90.20363236186.36576939922020
31.2531.2531.2590.2
72.702256466770.487736109586.940
62.562.562.588.1
51.62355531136.975573682463.480
12512512583.8
11.55751238321.17071105321.3160
25025025075.3
8.1452944414210320
50050050065.6
10001000100039.8
T-2
T-18
T-5
T-10
90.20363236186.36576939922020
31.2531.2531.2590.2
72.702256466770.487736109586.940
62.562.562.588.1
51.62355531136.975573682463.480
12512512583.8
11.55751238321.17071105321.3160
25025025075.3
8.1452944414210320
50050050065.6
10001000100039.8
T-2
T-18
T-5
T-10
65.288667141855.422343324371.7872968981
42.551674982240.217983651257.9025110783
23.307198859621.035422343345.3471196455
9.764789736310.13623978213.29394387
0.30.051.2
100010001000
T-2
T-18
T-5
91.378184193393.609022556461.8
79.229261920380.236305048359.2
55.649902024863.963480128933.3
18.354016982438.936627282510.8
11151
100010001000
T-2
T-18
T-5
100100100
101010
91.378184193393.609022556461.8
79.229261920380.236305048359.2
55.649902024863.963480128933.3
18.354016982438.936627282510.8
11151
T-2
T-18
T-5
100100100
101010
65.288667141855.422343324371.7872968981
42.551674982240.217983651257.9025110783
23.307198859621.035422343345.3471196455
9.764789736310.13623978213.29394387
0.30.051.2
T-2
T-18
T-5
Pim-1Pim-1
T-2T-18T-5No.50um100T-2T-18T-5No.5
01001001001000.4um
0.8um91.3781841933
0.41.6um79.2292619203
3.2um55.6499020248
0.891.378184193393.609022556461.869.96.4um18.35401698242091.378184193393.609022556461.869.9
12.8um11
1.679.229261920380.236305048359.264.64079.229261920380.236305048359.264.6
3.255.649902024863.963480128933.366.68055.649902024863.963480128933.366.6
6.418.354016982438.936627282510.814.216018.354016982438.936627282510.814.2
12.8111512320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-2T-18T-5No.5
0100100100100
1097.7225672878
2065.288667141855.422343324371.787296898185.50724637681.51511035652065.288667141855.422343324371.787296898185.5072463768
4.5499232129
4042.551674982240.217983651257.902511078390.37267080754042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.09109730858023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.55900621121609.764789736310.13623978213.2939438710.5590062112
3200.30.051.223200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
Pim-1Pim-1
T-2T-18T-5No.5T-10T-2T-18T-5No.5
0100100100100100
1098.7639286367
2091.378184193393.609022556461.869.996.63277111372091.378184193393.609022556461.869.9
4079.229261920380.236305048359.264.693.95360165624079.229261920380.236305048359.264.6
8055.649902024863.963480128933.366.689.32594532068055.649902024863.963480128933.366.6
16018.354016982438.936627282510.814.280.983985873516018.354016982438.936627282510.814.2
32011151278320111512
1000
Pim-2Pim-2
T-2T-18T-5No.5T-10T-2T-18T-5No.5
0100100100100100
1097.722567287899.3021148036
2065.288667141855.422343324371.787296898185.507246376898.28801611282065.288667141855.422343324371.787296898185.5072463768
4042.551674982240.217983651257.902511078390.372670807591.13796576034042.551674982240.217983651257.902511078390.3726708075
8023.307198859621.035422343345.347119645582.091097308593.05135951668023.307198859621.035422343345.347119645582.0910973085
1609.764789736310.13623978213.2939438710.559006211288.51963746221609.764789736310.13623978213.2939438710.5590062112
3200.30.051.2288.53200.30.051.22
1000
Pim-3Pim-3
T-2T-18T-5No.5T-10T-2T-18T-5No.5T-10
0100100100100100
1079.379.3
2090.20363236186.36576939922090.20363236186.3657693992
31.2590.231.2590.2
4072.702256466770.487736109586.961.74072.702256466770.487736109586.961.7
62.588.162.588.1
8051.62355531136.975573682463.449.68051.62355531136.975573682463.449.6
12583.812583.8
16011.55751238321.17071105321.312.216011.55751238321.17071105321.312.2
25075.325075.3
3208.1452944414210.03208.1452944414210.0
50065.650065.6
100039.8100039.8
No.5T-2T-5T-10
0100100100100
2.5
5
1079.3
15.625
2074.178.7
31.2590.2
4061.771.786.9
62.588.1
8049.652.863.4
12583.8
16012.243.521.3
200
25075.3
32010.0
50065.6
100039.8
T-2
T-5
T-10
Small molecule compound (M)
% Pim-1 activity
T-2
T-5
T-10
Small molecule compound (M)
% Pim-2 activity
100100100
101010
90.2036323612020
31.2531.2590.2
72.702256466786.940
62.562.588.1
51.62355531163.480
12512583.8
11.55751238321.3160
25025075.3
8.145294441410320
50050065.6
1000100039.8
T-2
T-5
T-10
Small molecule compound (M)
% Pim-3 activity
79.3
90.20363236186.3657693992202020
31.2531.2531.2531.2590.2
72.702256466770.487736109586.961.740
62.562.562.562.588.1
51.62355531136.975573682463.449.680
12512512512583.8
11.55751238321.17071105321.312.2160
25025025025075.3
8.1452944414210320320
50050050050065.6
100010001000100039.8
T-2
T-18
T-5
No.5
T-10
65.288667141855.422343324371.787296898185.5072463768
42.551674982240.217983651257.902511078390.3726708075
23.307198859621.035422343345.347119645582.0910973085
9.764789736310.13623978213.2939438710.5590062112
0.30.051.22
1000100010001000
T-2
T-18
T-5
No.5
91.378184193393.609022556461.869.9
79.229261920380.236305048359.264.6
55.649902024863.963480128933.366.6
18.354016982438.936627282510.814.2
111512
1000100010001000
T-2
T-18
T-5
No.5
-
IC50 (mmol/L)Pim-3 Pim-1 Pim-2 AKT-1 AKT-2 T2T5T10AKT1/27892>2000nd9056>2000nd3350>2000nd1934 > 2000 > 2000 > 200031.58 72.47345 462T-2T-5PimAKT/PKB
-
Times after treatment with inhibitor (days)Cell proliferation ratioT-2T-5L3.6plT-10Miapaca-2T-2 T-5
Graph2
111110.04253569740.04253569740.03435430660.03435430660.01772834510.01772834510.04217008640.04217008640.04478683630.0447868363
1.58396946561.48892674621.31029986961.37201365191.12357723580.06651026960.06651026960.05680862690.05680862690.02727053540.02727053540.09486990550.09486990550.08728138640.0872813864
3.70394955193.09965928452.49103650592.37883959041.97235772360.16068660390.16068660390.13941260690.13941260690.16167179680.16167179680.2160529070.2160529070.18126982130.1812698213
6.51593096585.42589437824.76368970014.06399317412.67154471540.58544377080.58544377080.19262733950.19262733950.11723460880.11723460880.27284371680.27284371680.14263292540.1426329254
7.80866246277.32964224875.96561277715.23037542663.1878048780.12270772030.12270772030.14976955950.14976955950.34301639490.34301639490.25351876460.25351876460.29957998230.2995799823
DMSO
5mM
10mM
20mM
30mM
T2-20080318
T2
3000cells
1hDMSODMSOSDSDSDSDSDSDSD
average00.2797510.01925919690.06883201190.2752510.00903234930.03280911470.2852510.01087428160.03811525270.2742510.01087428160.03964375350.2932510.01918984110.06542734760.2922510.01658061120.05672463620.28910.01051982260.0364007701
10.453751.62169406720.02166987160.07744771820.460751.67362876860.01481834450.4661.63336838420.02023198790.377751.37714181550.01037223860.03781348370.361.22741220590.01602081980.05462263820.312251.06825179610.00699404510.0239276260.299251.0354671280.01697792680.0587471517
20.983.5025017870.08976636340.32082331451.151754.18361787140.04225616331.123753.93883631270.03664582740.87153.1771782720.04112177040.14991531310.637752.17439481760.038055880.12975069880.609252.08433116660.02338624950.08000769590.553251.91435986160.02099801580.072657494
31.8586.64045746960.0253113940.09046245181.937.01053396290.09447045391.90556.6789344550.10286722831.299254.73660226030.13111667830.47800466030.928253.16484827820.05496893060.18741537890.8172.79507355460.02814249460.09627948870.741752.56660899650.06590080930.228030482
42.159757.71890636170.1953567250.69820130452.1737.89320741010.13502345482.1077.38520855240.12561050911.5495.64710171350.04243426290.15470019281.035753.53136720080.05556002760.18943071120.89453.06021211080.02495996790.08539161120.8012.77162629760.05037856690.1743203006
5
2hDMSODMSOSDSDSDSDSDSDSD
average00.3782510.02789713250.3657510.01350.3682510.0132759180.356510.01957038580.3807510.02865164340.382510.02353012250.3722510.0185539753
10.6771.78958498550.03461213660.66251.81109896120.02483948470.62651.70105891940.02621068480.496251.39200561010.01488567540.4431.16334033610.02605123160.37850.98954248370.00675771160.352250.94614558150.026725456
21.851254.89360296060.17934208472.156755.89598141060.09896927132.0065.44664675540.08573991681.44454.05189340810.0833166650.95352.50393907560.06354263660.8752.28758169930.03430257520.7852.10851463870.0314536696
33.248.5646312450.10784556863.318259.0712137780.07145336473.205758.70418137390.04174026832.133255.98387096770.24104961451.35553.55961134450.08033471641.22553.20392156860.04782258881.08352.91028740260.0975995219
43.2838.67829764740.16426198593.31933333339.07417532350.06068223243.214258.72726038560.03738426592.618257.34431977560.06500961471.570754.12486869750.09140523331.3073.41699346410.04480327371.17953.16814396990.0798519463
5
T2-20080318
DMSO
1mM
2mM
4mM
6mM
8mM
10mM
T2
DMSO
1mM
2mM
4mM
6mM
8mM
10mM
T5-20080318
0.06883201190.06883201190.03964375350.03964375350.06542734760.06542734760.05672463620.05672463620.03640077010.0364007701
0.07744771820.07744771820.03781348370.03781348370.05462263820.05462263820.0239276260.0239276260.05874715170.0587471517
0.32082331450.32082331450.14991531310.14991531310.12975069880.12975069880.08000769590.08000769590.0726574940.072657494
0.09046245180.09046245180.47800466030.47800466030.18741537890.18741537890.09627948870.09627948870.2280304820.228030482
0.69820130450.69820130450.15470019280.15470019280.18943071120.18943071120.08539161120.08539161120.17432030060.1743203006
DMSO
4mM
6mM
8mM
10mM
T5
T2
DMSO
1h0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day
3000 cells0.2790.4520.9221.8281.8762.0810.2810.4411.1462.0342.2072.0860.2840.4911.1242.0571.9652.0560.2850.3750.8421.4341.5841.5140.3140.3640.6880.991.0531.1320.290.3110.6030.8050.8630.7940.2980.3230.5410.7620.8260.639
0.260.4730.9251.8682.3172.1910.2620.471.121.9762.0842.0810.2780.4711.1531.852.2711.9440.270.3910.8991.1961.5731.4370.3050.3810.5960.9581.0581.2170.270.3160.6020.7630.8970.8630.2940.2990.530.8260.8130.656
0.2740.4660.9611.8872.2482.1250.2770.4581.2131.8192.0522.0540.2780.4431.0721.8812.0922.0770.2810.3660.8311.1781.4891.3890.2750.3470.6290.8730.9541.1560.3010.3030.6430.7630.8940.8660.290.2840.570.6840.7270.713
0.3060.4241.1121.8492.1981.9550.2810.4741.1281.8912.3491.7940.3010.4591.1461.8342.11.7050.2610.3790.9141.3891.551.3840.2790.3480.6380.8921.0781.0810.3080.3190.5890.7370.9240.9520.2740.2910.5720.6950.8380.659
average0.279750.453750.981.8582.159752.0880.275250.460751.151751.932.1732.003750.285250.4661.123751.90552.1071.94550.274250.377750.87151.299251.5491.4310.293250.360.637750.928251.035751.14650.292250.312250.609250.7670.89450.868750.2890.299250.553250.741750.8010.66675
SD0.01925919690.02166987160.08976636340.0253113940.1953567250.09952554110.00903234930.01481834450.04225616330.09447045390.13502345480.14053795450.01087428160.02023198790.03664582740.10286722830.12561050910.17063118120.01087428160.01037223860.04112177040.13111667830.04243426290.06027160750.01918984110.01602081980.038055880.05496893060.05556002760.05645352070.01658061120.00699404510.02338624950.02814249460.02495996790.06470123650.01051982260.01697792680.02099801580.06590080930.05037856690.0320663375
DMSO
2h0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day
3000 cells0.3850.6661.7393.1533.0413.240.3790.6262.1653.3573.3893.2730.3680.6612.0443.2393.1843.1390.3770.491.4342.3212.6992.5510.4120.451.0391.4271.6131.7380.3840.3750.8691.1831.2481.1450.3880.3890.7631.121.1980.913
0.3470.7081.7343.3693.4043.3380.3470.6762.0973.2943.2913.2330.3540.6322.0743.1463.253.0130.3470.5161.4981.9262.6312.4270.3980.4760.8871.4231.6021.9150.3490.3860.8721.1241.3111.2560.3820.3550.7531.2051.1860.942
0.3680.7011.8183.2893.3293.3850.3670.6682.2933.233.2783.3060.3650.6021.8813.2093.183.180.3680.4811.3311.9242.5432.3720.3540.430.9341.2821.4351.8440.3950.3710.9211.1291.3121.2620.3730.3340.8111.0051.0711.022
0.4130.6332.1143.1493.3583.1850.370.682.0723.392( + )3.0470.3860.6112.0253.2293.2432.9120.3340.4981.5152.3622.62.3840.3590.4160.9541.291.6331.750.4020.3820.8381.0661.3571.4880.3460.3310.8131.0041.2630.958
average0.378250.6771.851253.243.2833.2870.365750.66252.156753.318253.31933333333.214750.368250.62652.0063.205753.214253.0610.35650.496251.44452.133252.618252.43350.380750.4430.95351.35551.570751.811750.38250.37850.8751.12551.3071.287750.372250.352250.7851.08351.17950.95875
SD0.02789713250.03461213660.17934208470.10784556860.16426198590.09095420090.01350.02483948470.09896927130.07145336470.06068223240.11574793010.0132759180.02621068480.08573991680.04174026830.03738426590.12213380640.01957038580.01488567540.0833166650.24104961450.06500961470.08181483160.02865164340.02605123160.06354263660.08033471640.09140523330.08357182540.02353012250.00675771160.03430257520.04782258880.04480327370.14393140730.01855397530.0267254560.03145366960.09759952190.07985194630.0460968184
T10-20080318
T5
3000cells
1hDMSODMSOSDSDSDSDSD
average00.3012510.01281600560.04253569740.293510.0100829890.03435430660.3067510.00543905630.01772834510.29310.01235583530.04217008640.307510.01377195220.0447868363
10.477251.58396946560.02003954420.06651026960.4371.48892674620.0166733320.05680862690.4021.31029986960.00836660030.02727053540.4021.37201365190.02779688230.09486990550.34551.12357723580.02683902630.0872813864
21.1163.70394955190.04841487370.16068660390.909753.09965928450.04091760010.13941260690.764252.49103650590.04960090720.16167179680.6972.37883959040.06330350170.2160529070.60651.97235772360.055740470.1812698213
31.963256.51593096580.17639420810.58544377081.59255.42589437820.05653612410.19262733951.46154.76368970010.0359675780.11723460881.190754.06399317410.0799432090.27284371680.82152.67154471540.04385962460.1426329254
42.352757.80866246270.03697183610.12270772032.151257.32964224870.04395736570.14976955951.830255.96561277710.105237430.34301639491.53255.23037542660.0742809980.25351876460.980253.1878048780.09212084450.2995799823
5
2hDMSODMSOSDSDSDSDSD
average00.394510.0201742410.3810.01845715760.3992510.01071991920.3852510.01840968950.3987510.0209184926
10.74251.88212927760.02768272630.644251.69539473680.0323457880.581751.45692461810.01135414760.592751.53841162730.04355360680.484251.21426780340.0415321161
22.08955.29657794680.08012282241.6344.30.09766609781.3513.38342098670.12547244051.183253.07098364910.1245749440.9542.39217652960.0942408263
33.1417.96197718630.07506441682.724257.16907894740.0679331782.601756.51577761080.0699350892.008255.21217233320.17580742311.137752.85293380140.0553014466
43.3028.37008871990.09215204832.971257.81907894740.04235071822.84557.12622088660.03931496752.528256.56177004930.09142346531.4733.69358074220.153859243
5
T10-20080318
0.04253569740.04253569740.03435430660.03435430660.01772834510.01772834510.04217008640.04217008640.04478683630.0447868363
0.06651026960.06651026960.05680862690.05680862690.02727053540.02727053540.09486990550.09486990550.08728138640.0872813864
0.16068660390.16068660390.13941260690.13941260690.16167179680.16167179680.2160529070.2160529070.18126982130.1812698213
0.58544377080.58544377080.19262733950.19262733950.11723460880.11723460880.27284371680.27284371680.14263292540.1426329254
0.12270772030.12270772030.14976955950.14976955950.34301639490.34301639490.25351876460.25351876460.29957998230.2995799823
DMSO
5mM
10mM
20mM
30mM
T10
DMSO
5mM
10mM
20mM
30mM
Sheet3
T5
DMSO
1h0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day
3000 cells0.3150.5031.0562.1762.3792.3340.3050.4190.9311.6372.0872.3120.3140.4090.8281.4951.7142.0460.280.3690.6811.1571.4831.7140.3250.310.6360.8230.9811.272
0.3090.481.1721.9312.3892.2370.2820.4590.8891.5862.1772.0970.3050.4030.7791.4151.9382.0680.3020.40.7711.0961.5311.6960.3120.3570.5730.7631.1081.373
0.2880.4551.1061.9972.332.1730.2980.4320.8641.5152.1592.2390.3010.390.7221.4521.7712.0810.3050.4020.621.2751.6381.7440.2960.3420.5480.8310.9371.389
0.2930.4711.131.7492.3132.0030.2890.4380.9551.6322.1822.0650.3070.4060.7281.4841.8982.0650.2850.4370.7161.2351.4781.6250.2970.3730.6690.8690.8951.387
average0.301250.477251.1161.963252.352752.186750.29350.4370.909751.59252.151252.178250.306750.4020.764251.46151.830252.0650.2930.4020.6971.190751.53251.694750.30750.34550.60650.82150.980251.35525
SD0.01281600560.02003954420.04841487370.17639420810.03697183610.13923690840.0100829890.0166733320.04091760010.05653612410.04395736570.11691414230.00543905630.00836660030.04960090720.0359675780.105237430.01444529910.01235583530.02779688230.06330350170.0799432090.0742809980.05053958840.01377195220.02683902630.055740470.04385962460.09212084450.0559545947
DMSO
2h0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day
3000 cells0.4170.7722.0073.1473.1713.110.4010.6091.7362.7953.0183.0450.4150.5891.5172.5442.8293.0240.3730.5381.1971.9352.5012.7990.4270.4251.0251.1271.4732.05
0.4060.7522.1993.0373.3293.0490.360.6871.5862.7422.9192.9840.3950.5911.3792.552.8832.9630.4010.61.3221.7942.4772.7360.4020.5070.8951.0641.6862.219
0.3790.7062.0693.2153.3213.120.3890.6451.5222.7282.9893.0950.3910.5661.2482.6932.7983.0260.4010.5891.0192.162.6642.8460.3850.4870.8531.1751.4052.262
0.3760.742.0833.1653.3873.1620.370.6361.6922.6322.9593.2820.3960.5811.262.622.8723.3030.3660.6441.1952.1442.4712.8960.3810.5181.0431.1851.3282.389
average0.39450.74252.08953.1413.3023.110250.380.644251.6342.724252.971253.10150.399250.581751.3512.601752.84553.0790.385250.592751.183252.008252.528252.819250.398750.484250.9541.137751.4732.23
SD0.0201742410.02768272630.08012282240.07506441680.09215204830.04663600180.01845715760.0323457880.09766609780.0679331780.04235071820.12860922720.01071991920.01135414760.12547244050.0699350890.03931496750.1521687660.01840968950.04355360680.1245749440.17580742310.09142346530.06818296460.02091849260.04153211610.09424082630.05530144660.1538592430.140030949
T10
3000cells
1hDMSODMSOSDSDSDSDSD
average00.27610.01954482030.07081456630.2732510.01396125590.05108399530.274510.01464012750.05333379780.271510.02074447720.07640691410.279510.00842614980.0301472264
10.418251.51539855070.02781336610.10077306550.4261.5587266740.02376271590.08694736880.437751.59471766850.02746361230.10004958940.426251.56998158380.0185360010.06827256360.420751.50536672630.02676284740.0957525846
21.0673.8659420290.02672077840.09681441461.025753.753201610.07300856110.26713706971.02353.72859744990.09654532610.35171339211.048753.86279926340.13724764720.5055161961.113.97137745970.07817928110.2797112027
31.8936.85869565220.0182938970.06628223541.968757.2036223930.12829490770.46942886082.019257.35610200360.10820774770.39419944522.0327.48434622470.12794009010.47123421792.02457.24329159210.1080138880.3864539821
42.235758.10054347830.22082779870.80010071982.21858.1174533480.08095471990.29621192782.288.3060109290.07285602240.26541356072.2078.12891344380.12563704340.4627515412.19757.8622540250.10992573250.3932942129
5
2hDMSODMSOSDSDSDSDSD
average00.3882510.02411603890.3782510.0154353490.3842510.03350994880.377510.02935415930.3812510.0221415898
10.623751.6063610610.03830905030.62051.64023261960.03827531840.6441.67577413480.04536518490.611751.62052980130.02860506950.591251.55061631260.0369898635
21.9615.05021890290.06082214511.88054.97092254820.13668820971.8844.90241998440.1782376691.915.0596026490.26020760942.03155.32782585890.151544273
33.225258.30607777490.0461040493.21166666678.48973477840.10511580923.29433333338.57229594930.07381959993.29458.72715231790.03040559163.33858.75557303960.0869741341
43.19458.2268864280.08624963773.16358.36241078510.05054700783.20758.34634400210.05310053363.123758.27483443710.02572126233.28758.62182008920.0574485277
5
0.07081456630.07081456630.03014722640.03014722640.07640691410.07640691410.05333379780.0533337978
0.10077306550.10077306550.09575258460.09575258460.06827256360.06827256360.10004958940.1000495894
0.09681441460.09681441460.27971120270.27971120270.5055161960.5055161960.35171339210.3517133921
0.06628223540.06628223540.38645398210.38645398210.47123421790.47123421790.39419944520.3941994452
0.80010071980.80010071980.39329421290.39329421290.4627515410.4627515410.26541356070.2654135607
DMSO
5mM
10mM
20mM
30mM
DMSO
5mM
10mM
20mM
30mM
T10
DMSO
1h0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day0day1day2day3day4day5day
3000 cells0.2560.4541.1061.9041.9412.1230.2620.4391.0071.9612.1182.160.2840.4391.0341.9362.2732.2820.2560.4291.2112.0322.0752.1170.2840.431.072.0662.0511.896
0.2830.3881.0621.8842.2412.2950.2650.4191.0481.7922.2152.3130.2860.4760.9462.0382.3092.1470.2620.4040.912.1842.3322.180.2850.4531.2262.0392.3131.83
0.2650.4231.0531.9122.2872.3360.2930.3960.9372.0382.3162.1070.2540.4150.9581.9382.1832.0540.2660.4490.9641.8712.1261.9970.2670.4091.0861.8712.1911.711
0.30.4081.0471.8722.4742.0770.2730.451.1112.0842.2252.2580.2740.4211.1562.1652.3552.2370.3020.4231.112.0412.2951.9870.2820.3911.0582.1222.2351.788
average0.2760.418251.0671.8932.235752.207750.273250.4261.025751.968752.21852.20950.27450.437751.02352.019252.282.180.27150.426251.048752.0322.2072.070250.27950.420751.112.02452.19751.80625
SD0.01954482030.02781336610.02672077840.0182938970.22082779870.1269366640.01396125590.02376271590.0
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