Choline kinase plays a key role in the regulation of membrane phospholipid synthesis and has oncogenic properties in vitro. The expression level of CHKα is increased in a large number of human humors [3]. MN58b is a CHKα inhibitor that inhibits phosphocholine synthesis and reduced cell growth through induction of apoptosis. The sensitivity of cells to MN58b is correlated to the expression of CHKα protein. In a panel of 12 PDAC cell lines, the IC50s of MN58b ranged from 0.23 to 3.2μM. The IC50s of MN58b for parental and resistant cells was 3.14 μM and 0.77 μM, respectively[4]. In the experiment with MDA-MB-231 cells, after 48-hour treatment with 6μM MN58b, the percentage of cells in G1 phase was statistically significantly increased, whereas the percentage of cells in S and G2 phases was decreased[5]. In murine models, the increased levels of CHKα significantly reduced survival of mice with bladder cancer, while after the treatment with MN58b at dose of 5mg/kg, i.p.. A significant inhibition of tumor growth was observed, as well as relevant increased in survival[6].
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