physachenolide c

Physachenolide C is a **small-molecule natural product** of the 17β-hydroxywithanolide class, originally isolated from _Physalis_ species. It is a **potent and selective inhibitor of the bromodomain and extra-terminal domain (BET) family of proteins** (BRD2, BRD3, BRD4), with increased selectivity for BD1 of BRD3 and BRD4. Physachenolide C functions both by **direct inhibition of BET proteins**—which are readers of acetyl-lysine histone modifications and transcriptional regulators—and as a molecular glue, **promoting proteasome-mediated degradation** of BRD3 and BRD4. The molecule arrests the cell cycle in the G0–G1 phase and induces apoptosis, with **demonstrated anti-tumor and immunomodulatory activity** across multiple cancer models, including prostate cancer, melanoma, and renal carcinoma. Mechanistically, physachenolide C sensitizes tumor cells to extrinsic apoptosis signals (e.g., TRAIL, poly I:C, TNF family ligands) by reducing anti-apoptotic cFLIP and Livin, enhancing T cell-mediated killing of cancer cells. It is more potent than several gold-standard pan-BET inhibitors in preclinical models and is being investigated for potential use in combination immunotherapies[1][3][4][5][7].

Other names

PCC17β-hydroxywithanolide c