PU141

PU141 is a selected pyridoisothiazolone HAT inhibitor. PU141 is selective toward CBP and p300. PU141 induces cellular histone hypoacetylation and inhibits growth of several neoplastic cell lines originating from different tissues. Anticancer activity^[1]. IC50 & Target: CBP/p300^[1] In Vitro: PU141 inhibits cell growth at micromolar concentrations in A431 (epidemoid carcinoma), A549 (alveolar basal epithelial adenocarcinoma), A2780 (ovarian carcinoma), HCT116 (epithelial colon carcinoma), HepG2 (hepatocellular carcinoma), MCF7 (breast carcinoma), SK-N-SH (neuroblastoma), SW480 (colon adenocarcinoma) and U-87MG (epithelial-like glioblastoma-astrocytoma)^[1].
PU141 causes both histone hypoacetylation and growth inhibition in vitro. PU141 (25 µM) leads to a decrease in SAHA-induced H3K14 and H4K8 hyperacetylation, whereas H3K9 and H4K16 acetylation levels remaine stable after co-treatment of HDAC and HAT inhibitor. The impact on histone acetylation is similar in both SK-N-SH and HCT116 cells^[1]. In Vivo: PU141 (25 mg/kg; administered once intraperitoneally for 24 days) exhibits a significant antitumor effects against neuroblastoma xenografts in vivo^[1].