MMV688766 (MMV 688766) is a small molecule displaying broad-spectrum fungicidal activity through perturbation of lipid homeostasis, inhibits the growth of four geographically distinct C. auris clades with MIC80 of 12.5-50 uM.
MMV688766 inhibits the growth of C. albicans, Candida glabrata, and C. neoformans with comparable potency to that observed against C. auris with MIC80 of 12.5-25 uM.
MMV688766 disrupts fatty acid homeostasis without directly inhibiting the canonical fatty acid synthase (FAS), induces accumulation of lipid droplets in C. auris and C. albicans in a dose-dependent manner.
Treatment of C. auris with MMV688766 (25 uM) leads to a reduction in fatty acid and sphingolipid intermediate levels as a result of delayed fatty acids synthesis.
Loss of function of the transcriptional regulator HAL9 confers resistance to MMV688766, in part through the upregulation of the lipid-binding chaperone HSP12, a response that appears to assist in tolerating MMV688766-induced stress.