Olorofim is a novel selective antifungal compound with inhibitory effect on Aspergillus fumigatus DHODH (IC50: 44 nM) and almost no inhibitory effect on human DHODH (>100 uM).Olorofim has good efficacy against various pathogenic filamentous and dimorphic fungi such as Penicillium spp, Dermatophilus spp and Fusarium spp.

Olorofim (0.004-0.125 mg/L) showed highly potent in vitro activity against dermatophytes and opportunistic moulds (MIC range of 0.004-0.125 mg/L) except for Alternaria alternata. Penicillium, and Talaromyces species and Trichophyton species exhibited a low geometric mean (GM) MIC (GM 0.027 mg/L and 0.015 mg/L, respectively) of olorofim. Importantly, a 2-12 dilution step decrease in in vitro activity of olorofim as compared with azoles was observed against Penicillium and Talaromyces. Notably, olorofim displayed potent in vitro activity against Trichophyton isolates including terbinafine-resistant and azole-resistant Trichophyton mentagrophytes/interdigitale with a modal MIC value of 0.008 mg/L. Further, azole-resistant A. fumigatus isolates harbouring mutations in azole target Cyp51A genes and several cryptic aspergilli displayed low MICs (range 0.004-0.03 mg/L) of olorofim.[2]

The in vivo efficacy of the drug was investigated, using a guinea pig model, experimentally infected with Microsporum gypseum. Typical skin lesions of dermatophyte infection were observed in the guinea pig model at 7 days postinoculation. Following 1 week of daily topical administration of olorofim, similar to the clotrimazole group, the skin lesions were resolved and normal hair growth patterns appeared.[1]