CJF-III-288

CJF-III-288 is a small-molecule CD4 mimetic compound (CD4mc) designed to sensitize HIV-1-infected cells to immune-mediated clearance. It works by binding to the Phe43 cavity of the HIV-1 envelope glycoprotein gp120, which triggers a conformational shift in the envelope spikes from a "closed" to an "open" state. This transition exposes highly conserved, CD4-induced (CD4i) epitopes that are typically shielded from the immune system. By exposing these targets, CJF-III-288 enables non-neutralizing antibodies (nnAbs) to bind and recruit natural killer (NK) cells to eliminate infected CD4+ T-cells via antibody-dependent cellular cytotoxicity (ADCC). Developed through a multi-institutional collaboration including Emory University, the University of Montreal, and the Dana-Farber Cancer Institute, CJF-III-288 has shown biological activity in reducing viral loads and intact proviral DNA in SHIV-infected rhesus macaque models.