NMS-P715 is the first selective, ATP-competitive and orally bioavailable MPS1 small-molecule inhibitor (IC50=8 nM) and selectively reduces cancer cell proliferation, leaving normal cells almost unaffected.
NMS-P715 is a selective MPS1 inhibitor with an IC50 of 182 nM. It is highly specific, affecting no kinases below a 5 μM IC50 and only inhibiting CK2, MELK, and NEK6 under 10 μM. NMS-P715 triggers a significant spindle assembly checkpoint (SAC) bypass with an EC50 of 65 nM. At 1 μM, it accelerates mitosis in U2OS cells expressing YFP-α-tubulin, leads to aneuploidy, and suppresses HCT116 cell proliferation. Additionally, NMS-P715 (0.5, 1 μM) impacts the stability of the mitotic checkpoint complex (MCC) and cdc20 ubiquitination[1]. NMS-P715 (1 μM) enables spindle assembly checkpoint bypass and induces apoptosis in pancreatic ductal adenocarcinoma (PDAC) cell lines. Additionally, NMS-P715 (0-25 μM) selectively curtails the growth of PDAC cells[2].
体内研究
NMS-P715 (10 mg/kg) demonstrates 37% oral bioavailability and favorable pharmacokinetics in nude mice with human tumor cell xenografts implanted subcutaneously. At a dose of 90 mg/kg orally, NMS-P715 is well tolerated without causing body weight loss or noticeable toxicities in an A2780 ovarian carcinoma xenograft model. Furthermore, NMS-P715 (100 mg/kg, orally) reduces tumor growth by approximately 43% in the A375 melanoma xenograft model[1].
体外研究
NMS-P715 is a selective MPS1 inhibitor with an IC50 of 182 nM. It is highly specific, affecting no kinases below a 5 μM IC50 and only inhibiting CK2, MELK, and NEK6 under 10 μM. NMS-P715 triggers a significant spindle assembly checkpoint (SAC) bypass with an EC50 of 65 nM. At 1 μM, it accelerates mitosis in U2OS cells expressing YFP-α-tubulin, leads to aneuploidy, and suppresses HCT116 cell proliferation. Additionally, NMS-P715 (0.5, 1 μM) impacts the stability of the mitotic checkpoint complex (MCC) and cdc20 ubiquitination[1].
NMS-P715 (1 μM) enables spindle assembly checkpoint bypass and induces apoptosis in pancreatic ductal adenocarcinoma (PDAC) cell lines. Additionally, NMS-P715 (0-25 μM) selectively curtails the growth of PDAC cells[2].
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