F-901318

SKU: orb1700624

Description

Olorofim (F-901318) is a novel antifungal agent that selectively inhibits fungal dihydroorotate dehydrogenase (DHODH), demonstrating potent activity against Aspergillus fumigatus (IC50: 44 nM) with high selectivity over the human enzyme. It shows efficacy in vitro and in vivo against various pathogenic molds, including Aspergillus, Penicillium, and Fusarium species, supporting its research in antifungal development.

Research Area

Infectious Disease & Virology, Metabolism Research

Key Properties

• CAS Number: 1928707-56-5
• MW: 498.55
• Purity: 99.28%
• Formula: C₂₈H₂₇FN₆O₂
• SMILES: C(C(NC1=CC=C(C=C1)N2CCN(CC2)C=3N=CC(F)=CN3)=O)(=O)C4=C(C=C(C)N4C)C5=CC=CC=C5
• Target: Dehydrogenase,Antifungal
• Solubility: DMSO: 50 mg/mL (100.29 mM), Sonication is recommended.

Bioactivity

• Target IC50:
  Trichophyton isolates:0.008 mg/L(MIC)|Penicillium:0.027 mg/L(MIC)|Dermatophytes and opportunistic moulds:0.004-0.125 mg/L(MIC)|Cryptic aspergillis:0.004-0.03 mg/L(MIC)|Talaromyces species/Trichophyton species:0.015 mg/L(MIC)
• 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. 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.
• 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). 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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Olorofim, F901318, F-901318, F 901318, Fungal, DHODH

Compound Identifiers

PubChem CID

91885568