Danusertib (PHA-739358) (C007B-136825)

InformationDanusertib (PHA-739358) is anAurora kinaseinhibitor forAurora A/B/CwithIC50of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib inducesapoptosis, cell cycleIn vitroDanusertib inhibits the activities of other kinases such as FGFR1, Abl, Ret and Trka, with IC50 of 47 nM, 25 nM, 31 nM and 31 nM, respectively. In a cell assay, after treatment of wild-type and p53-deficient MEFs with Danusertib, the wild-type cells undergo an arrest in mitosis (4N) that is maintained for up to 48 h. The p53-deficient cells on the other hand do not arrest at the 4N DNA stage, but continues with additional rounds of DNA synthesis to become >8N. Treatment with Danusertib results in an increase in p53 protein levels and an associated increase in p21 protein, which is known to be transcriptionally regulated by p53. Increasing concentrations of Danusertib produces a dose-dependent reduction of cell growth after 48 hours in BCR-ABL-positive (K562, BV173) and BCR-ABL-negative (HL60) cells.In vivoAdministration of 25 mg/kg Danusertib (b.d. i.v.) to HL-60 xenograft rats results in 75% inhibition of tumor growth with complete regression in one animal. Danusertib results in biomarker modulation accompanied by inhibition of tumor growth. This is compatible with an expected mechanism of action of aurora kinase inhibition. Danusertib significantly inhibits proliferation of K562 cells and virtually suppressed tumor growth during the 10-day treatment period.Cell Datacell lines：Concentrations：5 μMIncubation Time：5 daysPowder Purity:≥95%. Specification: 10mM in DMSO Molecular Formula: C26H30N6O3 Molecular Weight: 474.55