| Name | Olorofim |
| Description | 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. |
| In vitro | 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] |
| In vivo | 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] |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 50 mg/mL (100.29 mM), Sonication is recommended.
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| Keywords | Fungal | F 901318 | DHODH |
| Inhibitors Related | Calcium Propionate | Dehydroacetic acid sodium | Potassium gluconate | D-Gluconic acid (solution) (50% in H2O) | Sulfacetamide sodium | Benzyl propionate | Terbinafine hydrochloride | Benzyl alcohol | Sodium formate | Magnesium acetate tetrahydrate | Geraniol | L-Citronellol |
| Related Compound Libraries | Ferroptosis Compound Library | Mitochondrial Membrane Protein-Targeted Compound Library | Bioactive Compound Library | ReFRAME Related Library | Anti-Fungal Compound Library | Drug Repurposing Compound Library | Mitochondria-Targeted Compound Library | Immunology/Inflammation Compound Library | Clinical Compound Library | Bioactive Compounds Library Max | Fluorochemical Library | Anti-Infection Compound Library |
United States
