Correlation between PAMPA permeability and cellular activities of hepatitis C virus protease inhibitors.

Correlation between PAMPA permeability and cellular activities of hepatitis C virus protease inhibitors. Research Abstract Details 

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Correlation between PAMPA permeability and cellular activities of hepatitis C virus protease inhibitors. Abstract Text:

Cheng Li,Latha Nair,Tongtong Liu,Fangbiao Li,John Pichardo,Sony Agrawal,Robert Chase,Xiao Tong,Annette S Uss,Stephane Bogen,F George Njoroge,Richard A Morrison,K-C Cheng,Cheng Li,Latha Nair,Tongtong Liu,Fangbiao Li,John Pichardo,Sony Agrawal,Robert Chase,Xiao Tong,Annette S Uss,Stephane Bogen,F George Njoroge,Richard A Morrison,K-C Cheng,

Parallel artificial membrane permeability assay (PAMPA) and Caco-2 cells have been frequently used for the evaluation of in vitro permeability of new chemical entities. In this study we evaluated the correlation between permeability, assessed by both methods, and the cellular potency of 34 novel hepatitis C virus (HCV) protease inhibitors. Two types of assays were used to determine the potency of HCV protease inhibitors: a cell-free assay that evaluates the intrinsic affinity (K(i)) between the protease and the inhibitor and a cell-based replicon assay that determines the inhibitors' IC(90). When the K(i)/IC(90) ratios were compared with the PAMPA permeability and the Caco-2 permeability by linear regression analysis, a reasonable correlation was found between the K(i)/IC(90) ratio and PAMPA permeability (r(2)=0.76) but not with Caco-2 permeability (r(2)=0.29). Correlations were also assessed between K(i)/IC(90) ratios and the following physico-chemical properties: logP (r(2)=0.41), logD (r(2)=0.58), clogP (r(2)=0.13), and mlogP (r(2)=0.30). These results suggest that passive permeability may play a role in the uptake and cellular activity of these HCV protease inhibitors, and that PAMPA was more predictive of cellular activity than physico-chemical properties or Caco-2 permeability.

Correlation between PAMPA permeability and cellular activities of hepatitis C virus protease inhibitors. Publishing Authors By Initials

C Li,L Nair,T Liu,F Li,J Pichardo,S Agrawal,R Chase,X Tong,AS Uss,S Bogen,FG Njoroge,RA Morrison,KC Cheng,C Li,L Nair,T Liu,F Li,J Pichardo,S Agrawal,R Chase,X Tong,AS Uss,S Bogen,FG Njoroge,RA Morrison,KC Cheng,

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Correlation between PAMPA permeability and cellular activities of hepatitis C virus protease inhibitors. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochemical pharmacology

VOLUME: 75

Page Numbers: 1186-97

Journal Abbreviation: Biochem. Pharmacol.

ISSN: 0006-2952

DAY: 7

MONTH: 11

YEAR: 2007

Correlation between PAMPA permeability and cellular activities of hepatitis C virus protease inhibitors. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Correlation between PAMPA permeability and cellular activities of hepatitis C virus protease inhibitors.

AFFILIATION: Schering-Plough Research Institute, K-15-2-2700, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.

Country: England

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MEDLINETA: Biochem Pharmacol

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