Tozasertib

Description	The Aurora kinases (A, B, and C) are a family of serine-threonine kinases that regulate various stages of mitotic function. With significant roles in cell cycle and cell division, Aurora kinase gene amplification and overexpression are linked to tumorigenesis. MK 0457 is a potent pan-Aurora kinase inhibitor but favors Aurora A (Ki = 0.6 nM) over Aurora B (Ki = 18 nM) or Aurora C (Ki = 4.6 nM). It shows selectivity against a panel of more than 190 different protein kinases. MK 0457 effectively inhibits proliferation of several different cell lines of clear cell renal carcinoma (IC50s < 10 µM) and blocks the growth of tumors in a rodent model of cancer (80 mg/kg), inhibiting histone H3 phosphorylation and increasing apoptosis. By depleting Aurora activity, MK 0457 disrupts bipolar spindle formation during mitosis, arresting cell cycle progression at the G2/M phase.
Pathways	Cell Cycle/DNA Damage Epigenetics
Targets	Aurora

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