CCT251455是有效和选择性的有丝分裂激酶单极纺锤体1(MPS1)抑制剂，IC50值为3nM。
CCT251455 is a potent and selective mitotic kinase monopolar spindle 1 (MPS1) inhibitor with an IC50 of 3 nM.
CCT251455 is a highly potent inhibitor of MPS1 that demonstrates high selectivity versus kinases tested in a broad kinome profiling panel. CCT251455 inhibits P-MPS1 with an IC50 of 0.04 μM in cell-based assay and has a GI50 of 0.16 μM[1].
CCT251455 demonstrates a good oral pharmacokinetic profile in mouse and rat as well as inhibition of MPS1 activity in vivo following oral administration[1].
[1]. Naud S, et al. Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1). J Med Chem. 2013 Dec 27;56(24):10045-65.
Cell experiment: | HCT116 cells are treated with 0-20 μM CCT251455 for 72 h. Cell viability is measured using the MTT assay[1]. |
Animal experiment: | Mice[1][1]Human HCT116 colon carcinoma cells are sc injected bilaterally in the flanks of female CrTac:NCr-Fox1(nu) athymic mice. Once tumors reach a mean diameter of 8 mm (day 15), mice are dosed twice at a 12 h intervals with 50, 75, or 100 mg/kg of CCT251455 in 10% (v/v) DMSO and 5% (v/v) Tween 20 in saline. Mice are culled (n=3 per group) at 2, 10, and 72 h after the second dose. Tumors are snap-frozen and stored at -80 °C until analysis[1]. |
参考文献: [1]. Naud S, et al. Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1). J Med Chem. 2013 Dec 27;56(24):10045-65. | |
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