Danusertib

Description	Danusertib 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.
Pathways	Angiogenesis/Protein Tyrosine Kinase Cell Cycle/DNA Damage Epigenetics
Targets	Src/Bcr Abl Aurora FGFR

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