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NMS-P715 NMS-P715 was found to be highly specific for MPS1, with no other kinases inhibited below an IC50 value of 5 mmol/L and with only 3 kinases inhibited below 10 mmol/L (CK2, MELK, and NEK6), which were not significantly affected by compound preincubation. NMS-P715 promotes massive SAC override with a half-maximal effective concentration (EC50) of 65 nmol/L. NMS-P715 accelerates mitosis and affects kinetochore components localization causing massive aneuploidy and cell death in a variety of tumoral cell lines and inhibits tumor growth in preclinical cancer models. Synonyms: NMS P715; NMS-P 715. Grades: >98%. CAS No. 1202055-32-0. Molecular formula: C35H39F3N8O3. Mole weight: 676.73. BOC Sciences 9
NMS-P715 Analog NMS-P715 is a selective and orally bioavailable MPS1 inhibitor, which selectively reduces cancer cell proliferation, leaving normal cells almost unaffected. NMS-P715 accelerates mitosis and affects kinetochore components localization causing massive aneuploidy and cell death in a variety of tumoral cell lines and inhibits tumor growth in preclinical cancer models. Inhibiting the SAC could represent a promising new approach to selectively target cancer cells. Synonyms: NMS-P715; NMSP715; NMSP-715; NMSP 715. Grades: 0.98. CAS No. 1202055-34-2. Molecular formula: C35H42N8O3. Mole weight: 622.774. BOC Sciences 9
MPS1 Inhibitor, NMS-P715 ( (N- (2, 6-diethylphenyl) -1-methyl-8- ({4-[ (1-methylpiperidin-4-yl) carbamoyl]-2- (trifluoromethoxy) phenyl}amino) -4, 5-dihydro-1H-pyrazolo[4, 3-h]quinazoline-3-carboxamide) ) An orally bioavailable, ATP-competitive, pyrazolo-quinazoline, MPS1 inhibitor (IC50=182nM, Ki=0.99nM) that is shown to act in a reversible and time-dependent manner. It demonstrates selectivity for MPS1 against a panel of 60 kinases, displaying activity against only three kinases, CK2, MELK, and NEK6 (<10uM), but not against other mitotic kinases including PLK1, CDK1, Aurora A, Aurora B, or the SAC kinase BUB1, in an in vitro kinase assay. It promotes massive SAC (spindle assembly checkpoint) override (EC50=65nM) in nocodazole-arrested U20S cells and elicits a reduction in the G1 and G2/M phase of the cell cycle in A2780 ovarian cancer cells, similar to RNAi-mediated MPS1 silencing. In addition, it is shown to inactivate SAC, delocalize kinetochore components, and inhibit the proliferation of select cancer cell lines (IC50 ~1uM), without marked activity among a panel of 127 normal cell lines. Also, it inhibits A2780 tumor xenograft growth in mice (90mg/kg/day, o.s., in vivo) by 53% witÂ… Group: Biochemicals. Grades: Highly Purified. Pack Sizes: 5mg. US Biological Life Sciences. USBiological 4
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