Synthesis of Danusertib

M.Wt: 474.55
Formula: C₂₆H₃₀N₆O₃
CAS No.: 827318-97-8

PHA-739358 (Danusertib) is a pyrrolopyrazole and small molecule Aurora kinases and Bcr-Abl kinase inhibitor with IC50 of 13, 79, and 61 nM for Aurora A, B, and C, respectively.
High activity was also observed against kinases known to be mutated or over expressed in different cancers such as Ret, Trk-A, and Abl (∼2-fold higher IC50 compared with Aurora A). Cross-reactivity with FGFR-1 was seen at a 4-fold higher IC50 compared with Aurora A. However, in another study, its specificity was tested in vitro against a broad panel of kinases representative of different kinase families. It was shown to be a potent inhibitor of all three Aurora kinases with IC50s of 27, 135, and 120 nM for Aurora A, B, and C, respectively.

Cortes-Franco J, Dombret H, Schafhausen P, et al. Danusertib hydrochloride (PHA-739358), a multi-kinase aurora inhibitior, elicits clinical benefit in advanced chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. Blood. 2009,114, 356.