Hanafi, Maha; Chen, Xinde; Neamati, Nouri published the artcile< Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91>, Recommanded Product: 4-Bromoisobenzofuran-1,3-dione, the main research area is tumorigenesis oncogenic pathways PROTACs STAT3 E3 ligase cytotoxicity degrader.
Napabucasin, undergoing multiple clin. trials, was reported to inhibit the signal transducer and transcription factor 3 (STAT3). To better elucidate its mechanism of action, we designed a napabucasin-based proteolysis targeting chimera (PROTAC), XD2-149(I) that resulted in inhibition of STAT3 signaling in pancreatic cancer cell lines without inducing proteasome-dependent degradation of STAT3. Proteomics anal. of XD2-149 revealed the downregulation of the E3 ubiquitin-protein ligase ZFP91. XD2-149 degrades ZFP91 with DC50 values in the nanomolar range. The cytotoxicity of XD2-149 was significantly, but not fully, reduced with ZFP91 knockdown providing evidence for its multi-targeted mechanism of action. The NQO1 inhibitor, dicoumarol, rescued the cytotoxicity of XD2-149 but not ZFP91 degradation, suggesting that the NQO1-induced cell death is independent of ZFP91. ZFP91 plays a role in tumorigenesis and is involved in multiple oncogenic pathways including NF-κB and HIF-1α.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Recommanded Product: 4-Bromoisobenzofuran-1,3-dione.
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