IST5-002 (N6-Benzyladenosine-5'-phosphate) is a selective Stat5a/b inhibitor with anticancer activity that inhibits the transcriptional activity of Stat5a/b and induces apoptosis and death of prostate cancer cells and chronic myelogenous leukemia (CML) cells, which can be used for cancer research.

STAT5b:3.5 μM, STAT5a:1.5 μM

IST5-002 is a potent Stat5a/b inhibitor that selectively blocks the transcriptional activity of Stat5a and Stat5b with IC50 values of 1.5 μM (Stat5a) and 3.5 μM (Stat5b), respectively.IST5-002 showed significant inhibitory effects on both Stat5a and Stat5b in a variety of cellular assays. Under different dosage and time conditions, IST5-002 was able to inhibit Bcr-Abl-induced Stat5a/b phosphorylation in K562 cells (0-40 μM, 3 h), Stat5a/b phosphorylation in T47D cells (5-100 μM, 2 h), and Stat5 dimerization and nuclear translocation in PC-3 cells, as well as inhibit the Stat5 target gene and DNA binding in COS-7 cells. In CWR22Rv1 and LNCaP cells, IST5-002 (2-50 μM, 48 h) significantly reduced the expression of Stat5a/b target genes such as Bcl-xL and cyclin D1. In addition, IST5-002 inhibited the growth of human prostate cancer cells by inducing apoptosis at high concentrations (3.1-50 μM, 72 hours) and triggered epithelial cell death in patient-derived prostate cancer samples cultured in vitro (25-100 μM, 7 days). IST5-002 (5 μM, 24-72 h) similarly inhibited Stat5a/b phosphorylation and induced apoptosis in Imatinib-sensitive and -resistant chronic granulocytic leukemia (CML) cells. [1]

Tumor growth was effectively inhibited in a prostate cancer xenograft model by intraperitoneal injection of 25-100 mg/kg IST5-002 once daily for 10 days. [1]