Recent developments of HSP90 inhibitors: an updated patent review (2020-present)

ABSTRACT

Introduction

The 90-kDa heat shock protein (HSP90) functions as a molecular chaperone, it assumes a significant role in diseases such as cancer, inflammation, neurodegeneration, and infection. Therefore, the research and development of HSP90 inhibitors have garnered considerable attention.

Areas covered

The primary references source for this review is patents obtained from SciFinder, encompassing patents on HSP90 inhibitors from the period of 2020 to 2023.This review includes a thorough analysis of their structural attributes, pharmacological properties, and potential clinical utilities.

Expert opinion

In the past few years, HSP90 inhibitors targeting ATP binding pocket are still predominate and one of them has been launched, besides, novel drug design strategies like C-terminal targeting, isoform selective inhibiting and bifunctional molecules are booming, aiming to improve the efficacy and safety. With expanded drug types and applications, HSP90 inhibitors may gradually becoming a sagacious option for treating various diseases.

KEYWORDS:

• Molecular chaperone
• HSP90
• small molecule inhibitor
• anti-cancer
• pimitespib

Article highlights

• HSP90 plays a crucial role in the regulation of numerous cellular proteins and is implicated in the pathogenesis of diverse diseases, including cancer and infection.

• Fungal selective HSP90 inhibitors for the treatment of invasive fungal infections have emerged.

• In 2021, HSP90α selective inhibitor Pimitespib was approved to treat gastrointestinal stromal tumors.

• New binding pockets and covalent binding sites have been discovered in HSP90 middle domain and C-terminal domain.

• Novel drug design strategies like bifunctional molecules expand applications of HSP90 inhibitors.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer received an honorarium from Expert Opinion on Therapeutic Patents for their review work but have no other relevant financial relationships to disclose. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.

Author contribution statement

Lei Wang and Qidong You conducted and organized the structure of the literature. Jianfeng Liu wrote and revised the manuscript. Huangliang Shu edited the manuscript. Qinxin Xia contributed to the figures.

Additional information

Funding

This study was supported by projects 82173741, 82003582 and 81930100 of the National Natural Science Foundation of China; BK20230103 of the Natural Science Foundation of Jiangsu Province; China Young Elite Scientists Sponsorship Program by CAST (2021QNRC001).