| Description | 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. |
| In vitro | Olorofim（0.004-0.125 mg/L）对皮肤癣菌和机会性霉菌展示出高度有效的体外活性（MIC范围0.004-0.125 mg/L），但对Alternaria alternata除外。Penicillium、Talaromyces种和Trichophyton种的几何平均MIC（分别为GM 0.027 mg/L和0.015 mg/L）较低。值得注意的是，与唑类化合物相比，Olorofim对Penicillium和Talaromyces的体外活性降低了2-12倍稀释步骤。特别是，Olorofim对包括对特比萘芬和唑类化合物耐药的Trichophyton mentagrophytes/interdigitale菌株，展示出强大的体外活性，模态MIC值为0.008 mg/L。此外，携带唑类化合物靶点Cyp51A基因突变的唑类化合物耐药A. fumigatus菌株和几种隐匿性曲霉的MIC值低（范围0.004-0.03 mg/L）。 |
| In vivo | 通过使用被Microsporum gypseum实验性感染的豚鼠模型，研究了该化合物的体内功效。在接种后7天，观察到豚鼠模型上典型的皮肤癣菌感染症状。经过每日一次的局部给药，持续1周后，发现皮损情况得到了解决，类似于clotrimazole组，正常的毛发生长模式重新出现。[1] |
| Target activity | 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) |
| Synonyms | Olorofim, F901318, F-901318 |
| molecular weight | 498.55 |
| Molecular formula | C28H27FN6O2 |
| CAS | 1928707-56-5 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 50 mg/mL (100.29 mM) |
| References | 1. Mirbzadeh Ardakani E, et al. Olorofim Effectively Eradicates Dermatophytes In Vitro and In Vivo. Antimicrob Agents Chemother. 2021;65(12):e0138621. 2. Oliver JD, Sibley GE, Beckmann N, Dobb KS, Slater MJ, McEntee L, du Pré S, Livermore J, Bromley MJ, Wiederhold NP, Hope WW, Kennedy AJ, Law D, Birch M. F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase. Proc Natl Acad Sci U S A. 2016 Oct 25. pii: 201608304. [Epub ahead of print] PubMed PMID: 27791100; PubMed Central PMCID: PMC5111691. 3. Singh A, et al. In vitro activity of the novel antifungal olorofim against dermatophytes and opportunistic moulds including Penicillium and Talaromyces species. J Antimicrob Chemother. 2021;76(5):1229-1233. 4. Lim W, et al. Madurella mycetomatis, the main causative agent of eumycetoma, is highly susceptible to olorofim. J Antimicrob Chemother. 2020;75(4):936-941. |