Discovery of novel Hsp90 C-terminal domain inhibitors that disrupt co-chaperone binding

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:38

Article

Mak, Oi Wei¹  Sharma, Nabangshu¹  Reynisson, Johannes^1,2  Leung, Ivanhoe K. H.^1,3 

[1] Univ Auckland, Sch Chem Sci, Private Bag 92019,Victoria St West, Auckland 1142, New Zealand

[2] Keele Univ, Sch Pharm & Bioengn, Hornbeam Bldg, Keele ST5 5BG, Staffs, England

[3] Univ Auckland, Maurice Wilkins Ctr Mol Biodiscovery, Private Bag 92019,Victoria St West, Auckland 1142, New Zealand

关键词: Hsp90;    Molecular chaperone;    Virtual screening;    Inhibitor;    Cancer;   

DOI  :  10.1016/j.bmcl.2021.127857

来源: Elsevier

【 摘 要 】

Heat shock protein 90 (Hsp90) is an essential molecular chaperone that performs vital stress-related and housekeeping functions in cells and is a current therapeutic target for diseases such as cancers. Particularly, the development of Hsp90 C-terminal domain (CTD) inhibitors is highly desirable as inhibitors that target the Nterminal nucleotide-binding domain may cause unwanted biological effects. Herein, we report on the discovery of two drug-like novel Hsp90 CTD inhibitors by using virtual screening and intrinsic protein fluorescence quenching binding assays, paving the way for future development of new therapies that employ molecular chaperone inhibitors.

【 授权许可】

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