设计合成一种新型选择性的口服有效苏氨酸酪氨酸激酶 (TTK) 抑制剂,PK研究均通过美迪西进行

Threonine tyrosine kinase (TTK), a dual-specificity protein kinase, acts as a core component of the spindle assembly checkpoint and plays a crucial role in accurate separation of sister chromatids during mitosis to avoid aneuploidy. TTK inhibition is an attractive wide-spectrum strategy for cancer therapy. Researchers designed and synthesized a series of pyrido[2, 3-d]pyrimidin-7(8H)-ones as new selective orally bioavailable TTK inhibitors. All the pharmacokinetic studies were carried out by Medicilon.Compounds 5o exhibits strong binding affinity to TTK with a Kd value of 0.15 nM.Compound 5o demonstrates good oral pharmacokinetic properties.Reference