体内
伊布替尼
生物利用度
体外
药品
溶解度
药代动力学
布鲁顿酪氨酸激酶
药理学
组合化学
化学
医学
生物
生物技术
生物化学
白血病
内科学
有机化学
慢性淋巴细胞白血病
受体
酪氨酸激酶
作者
Yonghui Sun,Zimo Yang,Zhimin Zhang,Zhen Li,Liubin Guo,Hao Pan,Xiang Liu,Dongzhou Liu,Yu Rao
出处
期刊:RSC medicinal chemistry
[The Royal Society of Chemistry]
日期:2023-01-01
卷期号:14 (8): 1562-1566
摘要
Ibrutinib is a first-line drug for the treatment of B-cell malignancies. BTKC481S mutation has led to drug resistance during clinical application. Herein, a novel BTK-targeting PROTAC molecule with better solubility and bioavailability was developed. Compound 15-271 has better solubility than ibrutinib and some reported BTK PROTACs. 15-271 has better liver microsomal stability than its analogues in multiple species. More importantly, 15-271 has a longer half-life and better bioavailability in vivo. The development strategy of compound 15-271 can be a general procedure for the optimization of other PROTACs.
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