Biological Activity
mk-8745 is a novel and selective inhibitor of aurora a with ic50 value of 0.6 nm [1].aurora a kinase is a member of mitotic serine/threonine kinases and plays an important role in cellular division by controlling chromatid segregation. it has been reported that abnormal expression of aurora a is correlated with the high occurrence of cancer and its expression determines cell sensitivity to mk-8745 treatment [1].mk-8745 is a potent aurora a inhibitor. when tested with p53-/+ cell lines, mk-8745 treatment induced apoptotic cell death in a p53-dependent manner through inhibiting aurora a activity [1]. in non-hodgkin lymphoma (nhl) cell lines, mk-8745 treatment arrested cell cycle in g2/m phase and induced cell death via inhibiting aurora a kinase [2]. in hct 116 puma (-), hct116 p21 (-), hct116 bax(-) and hct116 chk2(-) cell lines, mk-8745 treatment induced cell apoptosis with the percent of 25%, 22%, 25%, and 22%, respectively [3].in female athymic nude mice model subcutaneous xenografted with hct116 puma (-), hct116 p21 (-), hct116 bax(-) and hct116 chk2(-) cells, administration of mk-8745 significantly inhibited tumor growth [3].
References
[1]. nair, j.s., a.l. ho, and g.k. schwartz, the induction of polyploidy or apoptosis by the aurora a kinase inhibitor mk8745 is p53-dependent. cell cycle, 2012. 11(4): p. 807-17.
[2]. chowdhury, a., s. chowdhury, and m.y. tsai, a novel aurora kinase a inhibitor mk-8745 predicts tpx2 as a therapeutic biomarker in non-hodgkin lymphoma cell lines. leuk lymphoma, 2012. 53(3): p. 462-71.
[3]. shionome, y., et al., integrity of p53 associated pathways determines induction of apoptosis of tumor cells resistant to aurora-a kinase inhibitors. plos one, 2013. 8(1): p. e55457.
