Temsavir

Description

BMS 626529 is an inhibitor of HIV-1 attachment. It binds to non-ligand bound HIV-1 gp120 to inhibit HIV-1 interaction with host CD4⁺ T cells and subsequent HIV-1 binding and cell entry. BMS 626529 reduces infectivity of laboratory strains and clinical isolates of HIV-1 (EC₅₀s = 0.4-2,000 and 25-2,000 nM, respectively) with cytotoxic concentration (CC₅₀) values greater than 100 μM in a panel of mammalian cell lines.

Uses

Temsavir is a Fostemsavir (CAS# 864953-29-7) intermediate and an antiviral agent. It is an HIV-1 attachment inhibitor.

Uses

Temsavir is an FDA-approved HIV-1 adhesion inhibitor. It blocks the interaction of Env with CD4. This molecule also stabilises Env in a pre-fused 'closed' conformation, which is the preferred target of several broad-spectrum neutralising antibodies (bNAbs). temsavir treatment also reduces the ability of bNAbs to eliminate HIV-1 infected cells through antibody-dependent cellular cytotoxicity (ADCC). fostemsavir, a pre-drug of temsavir, was approved in the FDA on 2 July 2020 approved for the treatment of patients with multidrug-resistant HIV-1 infection.

brand name

BMS-626529

Biological Functions

Temsavir prevents the host cell receptor CD4 from interacting with Env by binding to the pocket under the gp120 β20-β21 ring of the Env subunit. It prevents viral entry and also stabilises Env in a 'closed' conformation^[3].

in vitro

the activity of bms-626529 is virus dependent, due to heterogeneity within gp120. bms-626529 had half-maximal effective concentration values of6 log10, with half-maximal effective concentration values in the low pm range against the most susceptible viruses. measurement of the binding affinity of bms-626529 for purified gp120 suggests that a contributory factor to its inhibitory potency may be a relatively long dissociative half-life [1].

target

HIV-1 subtype A envelope

References

[1] nowicka-sans b, gong yf, mcauliffe b, dicker i, ho ht, zhou n, eggers b, lin pf, ray n, wind-rotolo m, zhu l, majumdar a, stock d, lataillade m, hanna gj, matiskella jd, ueda y, wang t, kadow jf, meanwell na, krystal m.  in vitro antiviral characteristics of hiv-1 attachment inhibitor bms-626529, the active component of the prodrug bms-663068. antimicrob agents chemother. 2012;56(7):3498-507.
[2] nettles re, schürmann d, zhu l, stonier m, huang sp, chang i, chien c, krystal m, wind-rotolo m, ray n, hanna gj, bertz r, grasela d.  pharmacodynamics, safety, and pharmacokinetics of bms-663068, an oral hiv-1 attachment inhibitor in hiv-1-infected subjects. j infect dis. 2012;206(7):1002-11.
[3] MARIANNE BOUTIN. Temsavir Modulates HIV-1 Envelope Conformation by Decreasing Its Proteolytic Cleavage.[J]. Viruses-Basel, 2023. DOI:10.3390/v15051189.