Lenacapavir (GS-6207) sodium is an HIV-1 capsid inhibitor. Lenacapavir sodium binds to the interface between capsid hexamers and CA monomers, disrupts capsid assembly and viral maturation, inhibits nuclear translocation of HIV-1 DNA, interferes with CA-mediated protein-protein interactions, reduces the formation of 2-LTR circles and pre-integration proviruses, induces aberrant capsids, and decreases the production of mature HIV-1. Lenacapavir sodium exhibits activity against a variety of HIV-1 subtypes and clinical isolates. Lenacapavir sodium is applicable to research related to human immunodeficiency virus type 1 ( HIV-1 ) infection [1] [2] [3].
In Vivo, Lenacapavir sodium (subcutaneous; single dose) maintains plasma concentrations above the threshold needed for 95% HIV-1 replication inhibition for more than 12 weeks in rats[3]. Lenacapavir sodium (subcutaneous; single dose) maintains plasma concentrations above the threshold needed for 95% HIV-1 replication inhibition for more than 12 weeks in dogs[3].
In Vitro, Lenacapavir sodium inhibits HIV-1 with mean IC50 values of 200 pM in single-cycle assays and 170 pM in multicycle assays, and inhibits HIV-2 with mean IC50 values of 2.2 nM in single-cycle assays and 2.4 nM in multicycle assays[1]. Lenacapavir sodium inhibits HIV-1 in MT-4 cells with a mean EC50 of 105 pM[1]. Lenacapavir sodium inhibits HIV-1 in primary human CD4+ T cells with a mean EC50 of 32 pM and in primary human macrophages with a mean EC50 of 56 pM[1]. Lenacapavir sodium inhibits 23 HIV-1 isolates in PBMCs with a mean EC50 of 50 pM[1]. Lenacapavir sodium has its binding affinity reduced by 20-fold and viral susceptibility to it reduced by 10-fold due to the HIV-1 capsid N74D mutation[1]. Lenacapavir sodium (48 hours post-infection) exhibits reduced potency against HIV-1 with CA mutations associated with resistance, with fold resistance values ranging from 6-fold (Q67H) to >3226-fold (M66I) relative to wild-type HIV-1 in MT-2 cells[2].
References:
[1]. De Clercq E, et al. Lenacapavir: A capsid inhibitor for HIV-1 treatment and prevention. Biochem Pharmacol. 2025 Oct;240:117125.
[2]. Link JO, et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature. 2020;584(7822):614-618.
[3]. Singh K, et al. GS-CA Compounds: First-In-Class HIV-1 Capsid Inhibitors Covering Multiple Grounds. Front Microbiol. 2019;10:1227. Published 2019 Jun 20.
In Vivo, Lenacapavir sodium (subcutaneous; single dose) maintains plasma concentrations above the threshold needed for 95% HIV-1 replication inhibition for more than 12 weeks in rats[3]. Lenacapavir sodium (subcutaneous; single dose) maintains plasma concentrations above the threshold needed for 95% HIV-1 replication inhibition for more than 12 weeks in dogs[3].
In Vitro, Lenacapavir sodium inhibits HIV-1 with mean IC50 values of 200 pM in single-cycle assays and 170 pM in multicycle assays, and inhibits HIV-2 with mean IC50 values of 2.2 nM in single-cycle assays and 2.4 nM in multicycle assays[1]. Lenacapavir sodium inhibits HIV-1 in MT-4 cells with a mean EC50 of 105 pM[1]. Lenacapavir sodium inhibits HIV-1 in primary human CD4+ T cells with a mean EC50 of 32 pM and in primary human macrophages with a mean EC50 of 56 pM[1]. Lenacapavir sodium inhibits 23 HIV-1 isolates in PBMCs with a mean EC50 of 50 pM[1]. Lenacapavir sodium has its binding affinity reduced by 20-fold and viral susceptibility to it reduced by 10-fold due to the HIV-1 capsid N74D mutation[1]. Lenacapavir sodium (48 hours post-infection) exhibits reduced potency against HIV-1 with CA mutations associated with resistance, with fold resistance values ranging from 6-fold (Q67H) to >3226-fold (M66I) relative to wild-type HIV-1 in MT-2 cells[2].
References:
[1]. De Clercq E, et al. Lenacapavir: A capsid inhibitor for HIV-1 treatment and prevention. Biochem Pharmacol. 2025 Oct;240:117125.
[2]. Link JO, et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature. 2020;584(7822):614-618.
[3]. Singh K, et al. GS-CA Compounds: First-In-Class HIV-1 Capsid Inhibitors Covering Multiple Grounds. Front Microbiol. 2019;10:1227. Published 2019 Jun 20.