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.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Drug Design*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / chemistry*
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / enzymology*
  • Models, Molecular
  • Mutation
  • Nitriles / chemistry*
  • Protein Binding
  • Protein Conformation
  • Pyridazines / chemistry*
  • Pyrimidines / chemistry*
  • Rilpivirine


  • Nitriles
  • Pyridazines
  • Pyrimidines
  • etravirine
  • HIV Reverse Transcriptase
  • Rilpivirine

Associated data

  • PDB/3MEC
  • PDB/3MED
  • PDB/3MEE
  • PDB/3MEG