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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z6尊龙进行

2023-06-28
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7-TTK-inhibition-1.jpg

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

Minhao Huang, et al. Pyrido[2, 3-d]pyrimidin-7(8H)-ones as new selective orally bioavailable Threonine Tyrosine Kinase (TTK) inhibitors. Eur J Med Chem. 2021 Feb 5;211:113023. doi: 10.1016/j.ejmech.2020.113023.

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