R306465

R306465 (also known as JNJ-16241199) is a novel hydroxamate-based small molecule inhibitor of class I histone deacetylases (HDACs), with predominant activity against Histone deacetylase 1 (HDAC1) and Histone deacetylase 8 (HDAC8). Developed by Janssen Pharmaceutica, it exhibits broad-spectrum antitumor activity in preclinical models against both solid tumors—including ovarian, lung, colon, breast, and prostate cancer—and hematological malignancies such as leukemia and lymphoma. Mechanistically, R306465 induces histone H3 acetylation and upregulates p21waf1/cip1 expression leading to cell cycle arrest and apoptosis. It shows selectivity for class I HDACs over class IIb (notably poor inhibition of HDAC6), distinguishing it from other pan-HDAC inhibitors. In vivo studies demonstrate potent oral antitumoral efficacy in xenograft models. Clinical development has reached phase I trials for neoplasms[1][2][4][6].

Other names

N-hydroxy-2-(4-(naphthalen-2-ylsulfonyl)piperazin-1-yl)pyrimidine-5-carboxamide604769-01-9