MGCD290

MGCD290 is a first-in-class, orally available small molecule inhibitor of the fungal enzyme Hos2, a histone deacetylase (HDAC). Developed by MethylGene (later Mirati Therapeutics), it was designed to enhance the efficacy of azole antifungals such as fluconazole by reversing resistance in various fungal species. In vitro studies demonstrated that MGCD290 alone had modest activity against azole-resistant yeasts and limited activity against molds. However, when combined with azoles like fluconazole, posaconazole, or voriconazole, it showed synergistic effects—particularly notable in Candida species—by lowering the minimum inhibitory concentrations required for these antifungals. Clinical development included multiple Phase I trials showing good safety and no significant drug-drug interactions; a Phase II trial was conducted for vulvovaginal candidiasis (VVC). Development for mycoses and VVC has since been suspended[1][3][4][5][8].

Other names

Antifungal Hos2 histone deacetylase enzyme inhibitor