Information
CYC116 is a potent inhibitor ofAurora A/BwithKiof 8.0 nM/9.2 nM, is less potent to VEGFR2 (Kiof 44 nM), with 50-fold greater potency than CDKs, not active against PKA, Akt/PKB, PKC, no effect on GSK-3α/β, CK2, Plk1 and SAPK2A. Phase 1.
In vitro
The most Aurora-selective CYC116 shows inhibitory effect on Aurora A and B kinases 50-fold more potently than any of the CDKs assayed. CYC116 is initially screened against a panel of human leukemia and solid tumor cell lines using an MTT antiproliferative assay. The results show that CYC116 has broad-spectrum antitumor activity and shows specific cytotoxicity against the acute myelogenous leukemia cell line MV4-11 with IC50 of 34 nM. In addition, anti-proliferative activity of CYC116 is found to be associated with Aurora A and B modulation such as, inhibition of Aurora autophosphorylation, reduction of histone H3 phosphorylation, polyploidy, followed by cell death, resulting from a failure in cytokinesis.
In vivo
Mice bearing subcutaneous NCI-H460 xenografts are given CYC116 orally for 5 days, at dose levels of 75 and 100 mg/kg q.d. It leads to tumor growth delays of 2.3 and 5.8 days, which translated into specific growth delays of 0.32 and 0.81, respectively.
Cell Data
cell lines：K562 cell lines
Concentrations：0-10 μM
Incubation Time：72 or 96 hours
Powder Purity:≥98%
