- HIV reverse transcriptase (RT) remains a key molecular target and a cornerstone for HIV therapy.
- Yale researchers have identified catechol diether derivatives as novel, potent anti-HIV agents.
- These compounds are new non-nucleoside RT inhibitors (NNRTIs) that address continuing issues:
- concerning the possible emergence of new viral strains
- improved dosing
- long-term tolerability
- OCR5753 is the most potent anti-HIV agent with activity towards wild-type HIV-1; it inhibited replication of HIV-1 in infected human T-cells with an EC50 of 55 picomolar.
- OCR5753 is 10 times more potent than any NNRTI reported to date, including the newest FDA-approved drug, rilpivirine.
- Development of the catechol diethers can be expected to yield compounds with high therapeutic potential with low toxicity leading to a very high therapeutic index.
Frey, K. M., Gray, W. T., Spasov, K. A., Bollini, M., Gallardo‐Macias, R., Jorgensen, W. L., & Anderson, K. S. (2014). Structure‐Based Evaluation of C5 Derivatives in the Catechol Diether Series Targeting HIV‐1 Reverse Transcriptase. Chemical biology & drug design, 83(5), 541-549. [Pub Med]