molecules of the month

GSK3640254 is an HIV maturation inhibitor and Ph. IIb clinical candidate (60-180 mg PO QD) with activity against a range of HIV strains with Gag polymorphisms. The first HIV maturation inhibitor to read out clinically was bevirimat (Myriad Genetics), derived from a natural product first isolated from a Chinese herb. Maturation inhibitors like GSK3640254 work by binding to the cleavage site of the Gag protein, preventing release of p24 and formation of proper HIV capsids. Unfortunately, the initial drug was not efficacious enough due to polymorphisms in HIV Gag protein leading to resistance (response in only ~50% of patients). GSK had another clinical candidate, GSK3532795 in clinical trials, but this was discontinued due to GI tolerability issues in a Ph.…