Pre-ADME Predictive Screening
Transcript of 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.
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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.