compound 9c

Compound 9c (HEMTAC WEE1 degrader-1) is an investigational small molecule proteolysis-targeting chimera (PROTAC) belonging to a novel class of therapeutics known as HSP90-mediated targeting chimeras (HEMTACs). It was developed by the Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College in collaboration with Hainan Medical University specifically for the treatment of acute myeloid leukemia (AML). The drug functions by simultaneously binding to WEE1 G2 checkpoint kinase and Heat shock protein 90 (HSP90). Unlike traditional PROTACs that recruit E3 ligases like CRBN or VHL, HEMTACs leverage the HSP90 chaperone system to induce the targeted degradation of the WEE1 protein. Depletion of WEE1 leads to cell cycle arrest in the G2/M phase and subsequent apoptosis in cancer cells. Preclinical evaluations in patient-derived xenograft (PDX) models have shown that compound 9c exhibits high selectivity for AML cells and superior anti-cancer activity with lower hematotoxicity compared to the WEE1 inhibitor AZD1775.

Other names

HEMTAC WEE1 degrader-1