molecules of the month

Context. ICeD-2 (Merck) is a dipeptidyl peptidase 9 (DPP9) inhibitor under development for HIV-1 infections. Despite the significant advancements in antiretroviral therapy research leading to the approval of some highly effective treatments, the cure for HIV-1 infection has been elusive. A phenotypic screen looking at compound-induced HIV-1 infected cell kill using infected healthy donor PBMCs ultimately led to the tool compound ICeD-2, which was found to inhibit DDP9, an intracellular serine protease.Notably, the compound synergized with a high concentration of the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz that lowered the effective concentration of ICeD-2 to a clinically relevant dose at a concentration that could not induce total inhibition of DPP9. Complete inhibition of DPP9 is undesirable due to its hypothesized…