Olorofim（F-901318）is a novel selective antifungal compound targeting pyrimidine biosynthesis in mycobacteria, with inhibitory effect on Aspergillus fumigatus DHODH (IC50: 44 nM), but little inhibitory effect on human DHODH (>100 uM).Olorofim has good efficacy against a variety of pathogenic filamentous and dimorphic fungi, such as Penicillium spp, P. dermatitidis spp and Fusarium spp.

Talaromyces species/Trichophyton species:0.015 mg/L(MIC), Penicillium:0.027 mg/L(MIC), Cryptic aspergillis:0.004-0.03 mg/L(MIC), Trichophyton isolates:0.008 mg/L(MIC), Dermatophytes and opportunistic moulds:0.004-0.125 mg/L(MIC)

METHODS: 10 4 spores were suspended in 80 μl RPMI 1640 medium, buffered to pH 7.0 (with MOPS) and inoculated into 96-well microtiter plates. Then 20 μ Olorofim (F-901318) 0.0001-1 μg/ml was added to each well and the plates were incubated at 28°C. MICs were assessed by microtiter after 96 h of incubation.
RESULTS Dermatophytes were highly susceptible to Olorofim in vitro (MIC = 0.015–0.06 mg/L). [1]
METHODS: Olorofim was used to determine the in vitro antifungal activity of 246 azole-susceptible A. fumigatus isolates, 5 A. fumigatus isolates with TR34/L98H-mediated resistance, 19 Rhizopus isolates, 21 Fusarium species isolates, and one isolate each of 6 other fungi.
RESULTS Olorofim showed consistent antifungal activity against azole-susceptible A. fumigatus isolates (MIC50 = 0.008 μg/mL); all A. fumigatus isolates fell within the one- to two-fold dilution range of the MIC50 (0.008 μg/mL); five azole-resistant A. fumigatus isolates with Cyp51A-associated point mutations had MIC values ​​of 0.008 μg/mL. [3]

METHODS: A guinea pig model of dermatophytosis was established. Starting from the eighth day after infection, Olorofim（F-901318） (0.1 mg/ml in PEG300) was topically applied every day at a dose of 10 μg/lesion site for 7 days.
RESULTS Skin lesions resolved and normal hair growth pattern occurred. [1]
METHODS: Cyclophosphamide-immunosuppressed CD-1 mice infected with Scedosporium apiospermum, Pseudallescheria boydii (Scedosporium boydii), and Lomentospora prolificans were treated with intraperitoneal administration of olorofim (15 mg/kg every 8 hours for 9 days). The efficacy of olorofim treatment was assessed by survival 10 days post-infection, serum (1-3)-β-d-glucan (BG) levels 3 days post-infection, histopathology, and renal fungal burden.
RESULTS In olorofim-treated mice, serum BG levels were significantly suppressed, fungal DNA detected in target organs was significantly lower than in controls, and no or only a few bands were observed in histopathological observations of mouse kidneys. Lesions with hyphal elements. [2]