J Med Chem. 2010 May 27;53(10):4295-9. doi: 10.1021/jm1002233.

Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design.

Lansdon EB, Brendza KM, Hung M, Wang R, Mukund S, Jin D, Birkus G, Kutty N, Liu X.

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Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, California 94404, USA. eric.lansdon@gilead.com

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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Structures reported by this article

Hiv-1 K103n Reverse Transcriptase In Complex With Tmc278

PDB: 3MEG

Source: HIV-1 M:B_HXB2R

Method: X-Ray Diffraction

Resolution: 2.8 Å

See all 4 structures...

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Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and r...
Crystal structures of HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278): implications for drug design.
J Med Chem. 2010 May 27 ;53(10):4295-9. doi: 10.1021/jm1002233.

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