BAY1217389

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BAY 1217389 是一种有效的选择性单极纺锤体 1 (MPS1) 激酶抑制剂 (IC50<10 nM)。

BAY1217389 is an orally bioavailable, selective inhibitor of the serine/threonine kinase monopolar spindle 1 (Mps1, TTK), with potential antineoplastic activity. Upon administration, the Mps1 inhibitor BAY 1217389 selectively binds to and inhibits the activity of Mps1. This inactivates the spindle assembly checkpoint (SAC), accelerates mitosis, causes chromosomal misalignment and missegregation, and mitotic checkpoint complex destabilization. This induces cell death in Mps1-overexpressing cancer cells.

BAY 1217389 inhibits Mps1 kinase activity with IC50 value below 10 nM while showing an excellent selectivity profile. In cellular mechanistic assays BAY 1217389 abrogates nocodazole-induced SAC activity and induces premature exit from mitosis resulting in multinuclearity and tumor cell death. BAY 1217389 efficiently inhibits tumor cell proliferation in vitro.

BAY 1217389 achieves moderate efficacy in monotherapy in tumor xenograft studies. However, in line with its unique mode of action, when combines with paclitaxel, low doses of Mps1 inhibitor reduces paclitaxel-induced mitotic arrest in line with weakening of SAC activity. As a result, combination therapy strongly improves efficacy over paclitaxel or Mps1 inhibitor monotreatment at the respective MTDs in a broad range of xenograft models including those showing acquired or intrinsic paclitaxel-resistance. BAY 1217389 shows good tolerability without adding toxicity to paclitaxel monotherapy.

BAY1217389 | BAY-1217389 | BAY 1217389

Others

Other Targets

Mps1

Cancer

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1554458-53-5

561.5

C27H24F5N5O3

>98% (HPLC)

DMSO : ≥ 28 mg/mL; 49.87 mM

Cc1c(ccc(c1)c1cnc2n1nc(cc2NCCC(F)(F)F)Oc1c(c(c(cc1)OC)F)F)C(=O)NC1CC1

N-cyclopropyl-4-(6-(2,3-difluoro-4-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino)imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide

(-20℃)

With Ice Pack

≥ 2 years