Pre-ADME Predictive Screening

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DATA SHEET MultiScreen PAMPA and Permeability filter plates for 96-well predictive non-cell based assays Pre-ADME screening in 24-hours or less Predictive permeability assay results earlier in the drug discovery pipeline Automation compatible  Pre-ADME Predictive Screening Increase Drug Candidate and Library Screening Throughput Non-cell based 96-well assays are a fast, automation-friendly method for predictive drug candidate testing. High throughput MultiScreen filter plates can increase library screening 3–5x a day over IAM columns. Streamline The ADME Process Non-cell based assays dramatically streamline the ADME testing progress. They eliminate costly testing of unsuit- able transcellular compounds prior to Caco-2 tests. PAMPA 1,2 (parallel artificial membrane permeability assay) and permeability 3 assays can be performed in less than 24 hours and are automation compatible. They are a highly effective way to charac- terize and optimize lead candidates earlier in the drug discovery pipeline. Effective Predictive Outcomes MultiScreen PAMPA and Permeability filter plates are alternative strategies used to create 96 permeable membranes per plate. The artificial membranes are then treated with drug compounds to test for permeability. Passive transporter assays with results of known compounds (including testos- terone, sulfasalizene, and propranolol) correlate to Caco-2 published known ranges.

Transcript of Pre-ADME Predictive Screening

Page 1: Pre-ADME Predictive Screening

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MultiScreen™ PAMPA and Permeability filterplates for 96-well predictive non-cell basedassays

� Pre-ADME screening in24-hours or less

� Predictive permeabilityassay results earlier in thedrug discovery pipeline

� Automation compatible

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Pre-ADME PredictiveScreening

Increase Drug Candidate andLibrary Screening ThroughputNon-cell based 96-well assays are a

fast, automation-friendly method for

predictive drug candidate testing.

High throughput MultiScreen filter

plates can increase library screening

3–5x a day over IAM columns.

Streamline The ADME ProcessNon-cell based assays dramatically

streamline the ADME testing progress.

They eliminate costly testing of unsuit-

able transcellular compounds prior to

Caco-2 tests. PAMPA1,2 (parallel

artificial membrane permeability

assay) and permeability3 assays can

be performed in less than 24 hours

and are automation compatible. They

are a highly effective way to charac-

terize and optimize lead candidates

earlier in the drug discovery pipeline.

Effective Predictive OutcomesMultiScreen PAMPA and Permeability

filter plates are alternative strategies

used to create 96 permeable

membranes per plate. The artificial

membranes are then treated with drug

compounds to test for permeability.

Passive transporter assays with results

of known compounds (including testos-

terone, sulfasalizene, and propranolol)

correlate to Caco-2 published known

ranges.

Page 2: Pre-ADME Predictive Screening

Now you can buy Millipore products online @www.millipore.com/purecommerce

To Place an Order or ReceiveTechnical AssistanceFor additional information call yournearest Millipore office:

In the U.S. and Canada, call toll-free 1-800-MILLIPORE (1-800-645-5476)In the U.S., Canada and PuertoRico, fax orders to 1-800-MILLIFX(1-800-645-5439)Internet: www.millipore.comTech Service:

www.millipore.com/techservice

Millipore is a registered trademark of Millipore Corporation.

MultiScreen is a trademark of Millipore Corporation.

Lit. No. PF1781EN00

Printed in U.S.A. 1/02 02-015

Copyright 2002 Millipore Corporation, Bedford, MA. Allrights reserved.

Ordering Information

Materials for membrane treatment are provided by labs.

Description Qty/Pk Catalogue No.

MultiScreen-IP for PAMPA assays (no underdrain) 10/pk ELIIP 10 SSP

MultiScreen-IP for PAMPA assays (with underdrain) 10/pk MAIP N4 510

MultiScreen Permeability plate 10/pk MAPB MN 310

Accessories

The PTFE acceptor plate has been shown to improve final analysis results

depending on charge of transported small molecules. PTFE is shown to reduce

non-specific binding.

MultiScreen PTFE acceptor plate 1/pk MSSACCEPT0R

ReferencesThe following papers can be ordered

through your local Millipore office by

citing the RP literature number at the

end of each citation.

1. Kansey, Manfred et al, Physiochemical

High Throughput Screening: Parallel

Artificial Membrane Permeation Assay

in the Description of Passive Absorption

Processes. Journal of MedicinalChemistry 2001, Vol 41, No 7:

1007-1010 (Millipore: RP1011ENUS)

2. Sugano, Kiyohiko et al, High Through-

put Prediction of Oral Absorption:

Improvement of the Composition of the

Lipid Solution Used in Parallel Artificial

Membrane Permeation Assay. Journalof Biomolecular Screening 2001, Vol

6, No 3: 189-196 (Millipore:

RP1014ENUS)

3. Wohnsland, Frank and Faller, Bernard,

High-Throughput Permeability pH

Profile and High-Throughput Alkane/

Water log P with Artificial Membranes.

Journal of Medicinal Chemistry 2001,Vol 44, No 6: 923-930 (Millipore:

RP1013ENUS)

4. Gelo, M, Nielsen, P., The PAMPA

Story, pg 4, pION, Inc.

www.pampa2002.com/program

MultiScreen Filter Plate Selection

MultiScreen filter plates are available with membranes to support PAMPA and

Permeability assay requirements.

PAMPA Assays: MultiScreen-IP containing (PVDF) membrane is treated with a

lipid layer to create an artificial bio-membrane. Preliminary results show that

incorporating bio material in the artificial membrane yields reproducible results

for transcellular passive diffusion. By altering the mixture of phospholipids to

more resemble brush-border lipids, this model demonstrates improved oral

absorption predictive values of charged drugs.2,4 This can improve predictive

values for permeability results of charged compounds.

Permeability Assays: MultiScreen-Permeability containing PCTE membrane is

treated with a hexane/hexadecane treatment to categorize compound libraries

for permeability characteristics. This treatment is known to be high throughput

and yields predictive, passive drug absorption results when performing large

library screens.

PAMPA Permeability

Membrane IP (PVDF) PCTE

Plate material Acrylic Polystyrene

Artificial membrane Lipid layer Hexane/hexadecane

(treatment on filter)†

Acceptor plate material** PTFE PTFE

Assay time to analysis 2 – 15 hours 5 hours

Automation compatible Yes Yes

† MultiScreen filter plates are sold untreated. **PTFE acceptor plate sold separately. See ordering details.