GSK3732394

GSK3732394 is a multi-specific biologic developed as a novel, long-acting antiretroviral agent for HIV-1 infection. It is composed of three independent inhibitors of HIV entry within a single molecule, including an anti-CD4 adnectin and two gp41-targeting components (an adnectin and a peptide fusion inhibitor). The anti-CD4 adnectin binds to domains 2 and 3 of the CD4 receptor on human immune cells, inducing conformational changes that prevent HIV from binding to domain 1 via steric hindrance. The gp41-targeting elements block the viral fusion process by engaging the gp41 trimer spike during its transient exposure in viral entry. This combination provides three non-cross-resistant mechanisms for inhibiting HIV-1 entry. GSK3732394 was designed for subcutaneous administration as a long-acting therapy with potential self-administration. In preclinical models, it demonstrated potent antiviral activity comparable to standard-of-care antiretroviral regimens and showed minimal cross-resistance with existing therapies[1][2][6][8]. However, clinical development was terminated after Phase 1 due to pharmacokinetic/pharmacodynamic limitations that prevented achievement of desired therapeutic levels[1].

Other names

Combinectin