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Natural HSP90 inhibitors as a potential therapeutic intervention in treating cancers: A comprehensive review

热休克蛋白90 癌症 热休克蛋白 癌细胞 Hsp90抑制剂 药理学 药效学 生物 计算生物学 药代动力学 生物信息学 癌症研究 生物化学 遗传学 基因
作者
Hui Yi Liew,Xin Yoong Tan,Hong Chan,Kooi Yeong Khaw,Yong Sze Ong
出处
期刊:Pharmacological Research [Elsevier]
卷期号:181: 106260-106260 被引量:7
标识
DOI:10.1016/j.phrs.2022.106260
摘要

Heat shock protein 90 (Hsp90) has evolved as a cancerous cell growth regulator by stabilising various oncogenic kinases. Upon the Hsp90 inhibition, the expression of its client proteins is downregulated and thus leads to denaturation of cellular proteins and cancer cell death. Hsp90 inhibitors, particularly those naturally derived from plants, fungi and bacteria, have gained substantial interest as a feasible therapeutic approach for cancer treatment due to their diverse pharmacological properties. In order to gain insights into the potential development of more efficacious Hsp90 inhibitors for cancer treatment, this review is conducted to analyse both in vitro and in vivo data on the chemical and biological activities of natural Hsp90 inhibitors. The systematic search was conducted in databases (PubMed, Scopus and Web of Science) with terms "Hsp90 inhibitor" and "cancer", prompting a total of 61 articles after screening with inclusion criteria. This comprehensive review systematically summarised the efficacy of 14 different classes of naturally derived Hsp90 inhibitors in cancerous cell and animal tumour models by consolidating the primary outcomes in terms of IC50, reduction of tumour size and physicochemical properties. The detailed pharmacodynamic (the structure-activity relationship, mechanism of action) and pharmacokinetics (toxicity, oral bioavailability) of these Hsp90 inhibitors together with the study limitations were discussed. Collectively, these findings emphasise the necessity of comprehending the molecular mechanisms as well as the correlation of Hsp90 and its relative client proteins to drive the generation of viable Hsp90 inhibitors with improved pharmacodynamic and pharmacokinetic profiles.
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