Development of an in silico model for predicting efflux substrates in Caco-2 cells.

Development of an in silico model for predicting efflux substrates in Caco-2 cells. Research Abstract Details 

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Development of an in silico model for predicting efflux substrates in Caco-2 cells. Abstract Text:

Litai Zhang,Praveen V Balimane,Stephen R Johnson,Saeho Chong,

P-glycoprotein (P-gp) is an ATP dependent efflux transporter protein that has been demonstrated to play a critical role in affecting the absorption, metabolism, elimination and toxicity (ADMET) characteristics of a large number of marketed drugs. Therefore, it is important to evaluate whether or not compounds of interest are likely to interact with P-gp and/or other efflux transporters. An in silico efflux substrate (potential substrate of P-gp and or other transporters) classification model has been developed based on in vitro bi-directional Caco-2 cell permeability and five descriptors, using 14 marketed drugs and >100 discovery compounds synthesized at Bristol-Myers Squibb PRI. The model suggests that efflux substrates tend to contain electron deficient aromatic rings, are highly branched, and most contain tertiary nitrogen. This model demonstrated approximately 80% predictability of both non-substrates and substrates from a training set of 125 compounds. For a validation set of 46 compounds the predictability was approximately 72% for non-substrates and approximately 89% for substrates. The model has the potential to be used both as a filter for library designs to identify potential efflux substrates in early discovery as well as a primary screening methodology to identify the efflux substrate potential of drug candidates.

Development of an in silico model for predicting efflux substrates in Caco-2 cells. Publishing Authors By Initials

L Zhang,PV Balimane,SR Johnson,S Chong,

For similar pharmaceutical preparations research abstracts see: pharmaceutical preparations research

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Development of an in silico model for predicting efflux substrates in Caco-2 cells. Journal Published:

PUBLICATION TYPE: Validation Studies

Journal: International journal of pharmaceutics

VOLUME: 343

Page Numbers: 98-105

Journal Abbreviation:

ISSN: 0378-5173

DAY: 18

MONTH: 05

YEAR: 2007

Development of an in silico model for predicting efflux substrates in Caco-2 cells. Information

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LANGUAGE: eng

NlmUniqueID: 7804127

Development of an in silico model for predicting efflux substrates in Caco-2 cells. Keywords Mesh Terms:

KEYWORDS: Pharmaceutical Preparations

MESH TERMS: metabolism

Chemical & Substance for Abstract: Development of an in silico model for predicting efflux substrates in Caco-2 cells. Information

Substance Name: Pharmaceutical Preparations

Registry Number: 0

Grant and Affiliation Information for Development of an in silico model for predicting efflux substrates in Caco-2 cells.

AFFILIATION: Bristol-Myers Squibb Company PRI, Route 206 & Provinceline Road, P.O. Box 4000, Princeton, NJ 08543, USA. Litai.zhang@bms.com

Country: Netherlands

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MEDLINETA: Int J Pharm

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