AI Article Synopsis
- Newer HIV-1 maturation inhibitors, like VH3739937 (VH-937), have shown promise as effective antiretroviral treatments in clinical settings.
- VH-937 features a 4-cyanopyridyl ether design that is a step up from earlier inhibitors, leading to a better antiviral profile and effectiveness against the A364V mutation, a common resistance issue.
- Due to its improved pharmacokinetic properties, VH-937 has the potential for infrequent dosing, with initial human studies supporting the possibility of once-weekly administration.
Article Abstract
Newer generation HIV-1 maturation inhibitors have proven to be viable antiretroviral agents in the clinic. VH3739937, (VH-937, ) is an advanced HIV-1 maturation inhibitor (MI) with a 4-cyanopyridyl ether replacing the fluorine present in the previous lead MI GSK3640254 (GSK254, ). The introduction of aromatic methylene ethers α to the carboxylic acid moiety significantly enhanced the antiviral profile, with additional inhibitory effects observed toward the A364V mutation, the primary resistance mutation emerging in response to selective pressure by MIs. Structure-activity optimization led to the invention of VH-937, which combined the best overall antiviral profile with pharmacokinetic properties in animal models. These properties indicate the potential for infrequent dosing, a finding confirmed in initial clinical studies in humans that suggests its potential as a once-weekly dosing agent.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571082 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.4c00419 | DOI Listing |
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