Tasisulam

Tasisulam (LY 573636) is a small molecule antitumor agent that induces apoptosis via the intrinsic pathway, resulting in cytochrome c release and caspase-dependent cell death; shows antiproliferative effect against a variety of human hematopoietic malignancies, including AML, B-ALL, large B-cell and mantle cell lymphoma cell lines; promotes the recruitment of RBM39 to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation; causes aberrant pre-mRNA splicing.Blood Cancer Phase 1 Discontinued (In Vitro) :Tasisulam (200 nM-200 μM; 48 hours) induces an antiproliferative response across a wide range of tumor histologies with EC50s of 10 μM and 25 μM for Calu-6 and A-375 cell lines, respectively.Tasisulam (25, 50 μM; 72 hours) induces a concentration-dependent increase in 4N DNA and G2-M accumulation.Tasisulam (200 nM-200 μM; 48 hours) induces apoptosis in a broad range of in vitro cancer cell models.Tasisulam also blocks VEGF, epidermal growth factor, and fibroblast growth factor-induced endothelial cell cord formation.