tcsc0706 CCT 137690

CCT 137690 is a potent and orally available aurora kinase inhibitor with IC₅₀s of 15, 25, and 19 nM for aurora A, B and C, respectively.

IC50 & Target: IC50: 15 nM (Aurora A), 25 nM (Aurora B), 19 nM (Aurora C)^[1]

In Vitro: CCT 137690 displays antiproliferative activity in a range of human tumor cell lines, including SW620 colon carcinoma (GI₅₀=0.30 μM) and A2780 ovarian cancer cell line (GI₅₀=0.14 μM). CCT 137690 inhibits in vitro phosphorylation of histone H3. CCT 137690 is a moderate inhibitor of the hERG ion-channel (IC₅₀=3.0 μM)^[1]. CCT137690 efficiently inhibits histone H3 and TACC3 phosphorylation (Aurora B and Aurora A substrates, respectively) in HCT116 and HeLa cells. Continuous exposure of tumour cells to the inhibitor causes multipolar spindle formation, chromosome misalignment, polyploidy and apoptosis^[2].

In Vivo: CCT 137690 slows the growth of the SW620 xenografts with no observed toxicity^[1]. CCT 137690 significantly inhibits tumour growth in a transgenic mouse model of neuroblastoma (TH-MYCN) that overexpresses MYCN protein and is predisposed to spontaneous neuroblastoma formation^[2].