MK8353 (SCH900353) 是一种有效的、选择性的、可口服的 ERK1/2 抑制剂，IC50 分别为 23.0 nM 和 8.8 nM； MK8353 具有抗肿瘤活性。
MK-8353 is a potent, selective and orally available ERK1/2 inhibitor. It is a clinical candidate suitable for twice daily oral dosing as a potential new cancer therapeutic.
MK-8353 demonstrates kinase selectivity over a 227-human kinase panel; no additional kinase in the panel was inhibited by more than 35% at the 0.1 μM concentration, and only 3 kinases (CLK2, FLT4, and Aurora B) were inhibited >50% at the 1.0 μM concentration. MK-8353 shows potent antitumor activity against various cancer cell lines, such Malme-3M cells (Melanoma), Colo-205 cells (Colon), NCI-H292 cells (Lung), A-549 cells (NSCLC), 8505C cells (Thyroid), SW-626 cells (Ovarian), with EC50s of 21 nM, 19 nM, 130 nM, 230 nM, 210 nM, 108 nM.
MK-8353 administered by oral gavage at 60 mg/kg twice daily results in at least 50% tumor growth inhibition or regression in 83% of the animal models (including LOX, Colo-205, MIA PaCa-2, and Calu-6 cells).
参考文献
1. Moschos SJ, et al. Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors. JCI Insight. 2018 Feb 22;3(4). pii: 92352.
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