Barasertib, previously known as AZD1152-hydroxyquinazoline pyrazol anilide (HQPA), is a potent aurora kinase inhibitor, which is resulted from rapid phosphatase-mediated cleavage of the precursor, AZD1152, in serum following parenteral administration in vivo. It shows inhibitory effects against a broad range of aurora kinases, including aurora A kinase (AKB), aurora B kinase (ABK), and aurora C kinase (ACK) with inhibition constant (Ki) of 1369 nM, 0.36 nM, and 17.0 nM respectively, as well as the FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation. Barasertib has demonstrated anti-tumor activity against a range tumor cell lines including those of leukaemic acute myeloid leukemia (AML) origin.
Reference
Martin Grundy, Claire Seedhouse, Nigel H Russell and Monica Pallis. P-glycoprotein and breast cancer resistance protein in acyte myeloid leukaemia cells treated with the aurora-B kinase inhibitor barasertib-Hqpa. BMC Cancer 2011, 11:254
Mike Dennis, Michelle Davies, Stuart Oliver, Roy D’Souza, Laura Pike, and Paul Stockman. Phase I study of the aurora B kinase inhibitor barasertib (AZD1152) to assess the pharmacokinetics, metabolism and excretion in patients with acute myeloid leukemia. Cancer Chemother Pharmacol (2012) 70:461-469