☆ 4.7 Article

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

JOURNAL OF MEDICINAL CHEMISTRY (2010)

期刊

JOURNAL OF MEDICINAL CHEMISTRY

卷 53, 期 10, 页码 4295-4299

出版社

AMER CHEMICAL SOC

DOI: 10.1021/jm1002233

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Chemistry, Medicinal

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Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231]

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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 K 103N 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 TM C125 and differences in protein conformation for TMC278.

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