2. Academic Validation
  3. Lanosterol 14α-Demethylase (CYP51)/Heat Shock Protein 90 (Hsp90) Dual Inhibitors for the Treatment of Invasive Candidiasis

Lanosterol 14α-Demethylase (CYP51)/Heat Shock Protein 90 (Hsp90) Dual Inhibitors for the Treatment of Invasive Candidiasis

  • J Med Chem. 2025 Jan 23;68(2):1668-1681. doi: 10.1021/acs.jmedchem.4c02305.
Mingming Zhang 1,  Wanzhen Yang 1,  Na Liu 1,  Jie Tu 1,  Jingsheng Lin 2,  Guoqiang Dong 1,  Dongmei Zhao 2,  Chunquan Sheng 1
Affiliations

Affiliations

  • 1 The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China.
  • 2 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
PMID: 39754582 DOI: 10.1021/acs.jmedchem.4c02305
Abstract

Invasive candidiasis has attracted global attention with a high incidence and mortality. Current Antifungal drugs are limited by unfavorable therapeutic efficacy, significant hepatorenal toxicity, and the development of drug resistance. Herein, we designed the first generation of lanosterol 14α-demethylase (CYP51)/heat shock protein 90 (HSP90) dual inhibitors on the basis of Antifungal synergism. Among them, dual inhibitor MM4 exhibited potent in vitro and in vivo Antifungal activity against Candida albicans and effectively inhibited important Fungal virulence factors (e.g., hyphae, biofilm). Therefore, CYP51/HSP90 dual inhibitors show great promise in the development of novel Antifungal drugs to combat invasive candidiasis.

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