Biological Activity
PHA-680632 is an aurora kinase inhibitor with IC50s of 27, 135 and 120 nM for aurora A, B and C, respectively.
In Vitro
PHA-680632 shows 30- to 200-fold higher IC50s of FLT3, LCK, PLK1, STLK2, VEGFR2, and VEGFR3 compared with Aurora A. PHA-680632 has potent antiproliferative activity in a wide range of cell types. The IC50s are 0.32, 0.41, 0.06, 1.17, 0.56, 0.62, 0.29, 0.11, 1.56, 0.62, 0.07, 0.13, 0.41 μM for C33A, HeLa, HCT116, HT29, LOVO, A549, MCF7, A2780, U2OS, DU145, U937, HL60, NHDF. PHA-680632 can cause polyploidy in tumor cells. PHA-680632 cell treatment induces phenotypes similar to Aurora A or B depletion[1]. PHA680632, inhibits colony formation in different cancer cell lines and induced polyploidy. Aurora-A inhibition by PHA680632 enhances radiation response in cancer cells, especially in p53-deficient cells[2].
In Vivo
PHA-680632 suppresses tumor growth in animal models. PHA-680632 treatment at 45 mg/kg dose results in 85% of TGI without signs of toxicity in the HL60 human acute myelogenous leukemia xenograft model. PHA-680632 treatment at 60 mg/kg i.v. b.i.d. for 5 days results in 78% of TGI without signs of toxicity in the A2780 human ovarian carcinoma model[1]. PHA680632 in association with radiation leads to an additive effect in cancer cells, especially in the p53-deficient cells, but does not act as a radiosensitiser[2].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
