Non-nucleoside inhibitors of HIV-1 reverse transcriptase

Summary

Four years ago it became apparent that an allosteric site on HIV-1 reverse transcriptase was responsible for the enzyme inhibitory activity of a number of structurally diverse organic compounds. These molecules bear little resemblance to the endogenous substrate, deoxynucleotide triphosphates, and through kinetic measurements they were found to be noncompetitive inhibitors. When examined in cell culture, these compounds proved to be potent antiviral agents. Improvements made in the potency and pharmacodynamic properties of the early inhibitors quickly allowed evaluation of several compounds in a clinical setting. From these and other studies came a discouraging profile of rapidly emerging viral resistance. Further work in the field may show that a combination of these and other drugs may be of benefit in combatting AIDS.

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Young, S.D. Non-nucleoside inhibitors of HIV-1 reverse transcriptase. Perspectives in Drug Discovery and Design 1, 181–192 (1993). https://doi.org/10.1007/BF02171661

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Key words

  • AIDS
  • HIV-1
  • Reverse transcriptase
  • Non-nucleoside inhibitors