Table 4.

Current antifungal CYP51 inhibitors.

Name	Approval time	Clinical applications	Adverse effects	Remarks	References
Ketoconazole(KCZ)	1981	Oral, vaginal, cutaneous and systemic candidiasis	Liver damage, interference of the endocrine system, nausea, headache, abdominal pain, etc.	Oral formulation has withdrawn from Europe, Australia, and China.	10
Fluconazole(FCZ)	1988	Systemic Candida infection, cryptococcal meningitis, vaginal, oropharyngeal and esophageal candidiasis	Nausea, vomiting, abdominal pain, gastrointestinal adverse reactions, reversible mild liver necrosis and thrombocytopenia	Adjuvants such as calcineurin inhibitors, heat shock protein 90 inhibitors have been found	11
Itraconazole(ICZ)	1988	Invasive aspergillosis, superficial candidiasis, dermatophyte infection, sporotrichosis, blastomycosis, histoplasmosis, penicilliosis, and coccidioidomycosis, etc.	Gastrointestinal symptoms, cardiac failure, peripheral edema and hepatic inflammation		12
Voriconazole(VCZ)	2002	Aspergillosis, candidiasis, scedosporium, and Fusarium infection	Neurotoxicity, visual toxicity, hepatotoxicity and skin malignancy	Therapeutic drug testing (TDM) is required	13
Posaconazole(PCZ)	2006	Aspergillus and Candida infections, especially fluconazole or itraconazole resistant cases	Serious adverse reactions rarely exit. Non-serious adverse reactions include SeHeadache, nausea, and menstrual disorder, etc.		14
Isavuconazole	2015	Invasive aspergillosis and invasive mucormycosis	Nausea, vomiting, diarrhea and hepatobiliary toxicity		15

10: Listed, 1981; Heel et al., 1982; Pont et al., 1982, 1985; Daneshmend and Warnock, 1988; Chien et al., 1997; Rodriguez and Acosta, 1997; Rodriguez et al., 1999; Greenblatt et al., 2011; Yan et al., 2013; Greenblatt and Greenblatt, 2014; Gupta et al., 2014; Gupta and Lyons, 2015). 11: Washton, 1989; Morita et al., 1992; Amichai and Grunwald, 1998; Fischer et al., 2010; Liu et al., 2014; Behtash et al., 2017. 12: Isoherranen, 2004; Lestner and Hope, 2013; Abuhelwa et al., 2015. 13: Hyland et al., 2003; Wood et al., 2003; Espinel-Ingroff et al., 2012; Owusu et al., 2014; Malani et al., 2015; Job et al., 2016; Lamoureux et al., 2016; Levine and Chandrasekar, 2016; Patterson et al., 2016; Li et al., 2017; Xing et al., 2017; Cormican et al., 2018; Mounier et al., 2018. 14: Kim et al., 2003; Sansone-Parsons et al., 2007; Groll and Walsh, 2014; Clark et al., 2015; Moore et al., 2015. 15: Schmitt-Hoffmann et al., 2006; McCormack, 2015; Pettit and Carver, 2015; Traynor, 2015; Maertens et al., 2016; Denis et al., 2018; Ledoux et al., 2018.