Description
CCT137690 is a highly selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 15 nM, 25 nM and 19 nM. It has little effect on hERG ion-channel.
Storage
2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO.
Targets
Aurora A, Aurora B, Aurora C
Molecular Formula
C26H31BrN8O
Chemical Name
6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridine
Solubility
DMSO 4 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL
In vitro
CCT137690 displays antiproliferative activity in a range of human tumor cell lines, including SW620 colon carcinoma cell and A2780 ovarian cancer cell with GI50 of 0.3 and o.14 μM, respectively. In addition, CCT137690 also inhibit the phosphorylation of histone H3. CCT137690 inhibits the major cytochrome P450 isoforms (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP3A4) with IC50 greater than 10 μM. However, CCT137690 is a moderate inhibitor of the hERG ion-channel with IC50 of 3.0 μM. CCT137690 effectively inhibits the growth of human tumor cell lines of different origins with GI50 ranging from 0.005 to 0.47 μM. CCT137690 completely inhibits both Aurora A autophosphorylation at T288 and histone H3 phosphorylation at 0.5 μM. CCT137690 induces polyploidy, mitotic aberrations, and apoptosis in HCT116 cells. CCT137690 reduces MYCN levels and GSK3β phosphorylation in the KELLY neuroblastoma cell line.CCT137690 inhibits autophosphorylation of FLT3 and phosphorylation of its downstream targets STAT5 and p44/42 MAPK (Erk1/2).
In vivo
CCT137690 is highly orally bioavailable and inhibits the growth of SW620 colon carcinoma xenografts with no observed toxicities as defined by body weight loss. CCT137690 inhibits growth of MYCN-induced neuroblastoma at a dose of 100 mg/kg.Additionally, CCT137690 achieves target modulation and potently inhibits the growth of subcutaneous MOLM-13 xenografts, with no obvious toxicity or loss of body weight.
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