Crystal Structures of HIV-1 Reverse Transcriptase with Etravirine (TMC125) and Rilpivirine (TMC278): Implications for Drug Design

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2010 May 5

PMID 20438081

Citations 59

Authors

Eric B Lansdon

Katherine M Brendza

Magdeleine Hung

Ruth Wang

Susmith Mukund

Debi Jin

Gabriel Birkus

Nilima Kutty

Xiaohong Liu

Affiliations

Soon will be listed here.

Abstract

Diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitors (NNRTIs) have inherent flexibility, helping to maintain activity against a wide range of resistance mutations. Crystal structures were determined with wild-type and K103N HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278). These structures reveal a similar binding mode for TMC125 and TMC278, whether bound to wild-type or K103N RT. Comparison to previously published structures reveals differences in binding modes for TMC125 and differences in protein conformation for TMC278.

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