ABC1183 is a novel diaminothiazole that inhibits GSK3α, GSK3β and CDK9. ABC1183 inhibits the growth of a numerous cancer cell lines by decreasing cell survival by inducing G2/M arrest and through altering GSK3, glycogen synthetase, β-catenin phosphorylation and MCL1 expression,and is orally active.

GSK-3α:327 nM, GSK-3β:657 nM, CDK9-CyclinT1:321 nM

ABC1183 inhibits cell proliferation and tumor growth of various cancer types by specifically attenuating GSK3 and CDK9 activity. ABC1183 altered GSK3 activity as indicated by decreased GSK3α/β and GS phosphorylation and increased β-catenin phosphorylation[1].

Murine melanoma B16 tumors were propagated in C57BL/6 mice were treated with oral ABC1183 or vehicle. Tumor growth was decreased more than 70% within 8 days by ABC1183 treatment. On the basis of body weight, gross toxicities were not observed. ABC1183 was determined to suppress tumor growth in the absence of organ and hematopoietic toxicity. The expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were suppressed[1][2].