Z-Endoxifen-PROTAC

Z-Endoxifen-PROTAC (also known as ENDX-PROTAC or EPrC) is a first-in-class proteolysis-targeting chimera (PROTAC) small molecule series developed by the Mayo Clinic. It incorporates Z-endoxifen (the active metabolite of tamoxifen) as the targeting warhead and cereblon (CRBN) as the E3 ubiquitin ligase recruitment moiety. Although originally designed to target estrogen receptor alpha (ERα) and protein kinase C beta I (PKCβI), Z-Endoxifen-PROTAC compounds (such as lead candidates EPrC-007 and EPrC-009) have been shown to primarily target and degrade G to S phase transition protein 1 (GSPT1), a key translation termination factor. This degradation leads to potent anti-proliferative effects, apoptosis, and marked DNA double-strand breaks. Z-Endoxifen-PROTAC is being investigated for the treatment of triple-negative breast cancer (TNBC), including chemo-sensitive and chemo-resistant models, as well as other cancers such as leukemia, pancreatic cancer, lymphoma, lung cancer, melanoma, and ovarian cancer.

Other names

ENDX-PROTACENDX-PROTACsZ-endoxifen-PROTACendoxifen-PROTAC