当前位置: X-MOL 学术Bioorg. Med. Chem. Lett. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Design, synthesis and biological evaluation of 2-indolinone derivatives as PAK1 inhibitors in MDA-MB-231 cells.
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2020-06-20 , DOI: 10.1016/j.bmcl.2020.127355
Dahong Yao 1 , A Ruhan 2 , Jin Jiang 2 , Jian Huang 2 , Jinhui Wang 2 , Weina Han 2
Affiliation  

P21-activated kinase 1 (PAK1) plays a vital role in the proliferation, survival and migration of cancer cells, which has emerged as a promising drug target for cancer therapy. In this study, a series of 2-indolinone derivatives were designed and synthesized through a structure-based strategy. A potent PAK1 inhibitor (ZMF-005) was discovered, which presented an IC50 value of 0.22 μM against PAK1 with potent antiproliferative activity. Furthermore, we predicted the binding mode of ZMF-005 and PAK1 by molecule docking and dynamic (MD) simulation. In addition, ZMF-005 was documented to induce significant apoptosis and suppress migration in MDA-MB-231 cells. Collectively, these findings revealed that ZMF-005 is a novel potent PAK1 inhibitor for breast cancer treatment.



中文翻译:

设计,合成和生物学评估2-吲哚酮衍生物作为MDA-MB-231细胞中的PAK1抑制剂。

P21活化激酶1(PAK1)在癌细胞的增殖,存活和迁移中起着至关重要的作用,而癌细胞已成为一种有希望的癌症治疗靶标。在这项研究中,通过基于结构的策略设计和合成了一系列2-吲哚酮衍生物。发现了一种有效的PAK1抑制剂(ZMF-005),它对具有有效抗增殖活性的PAK1的IC 50值为0.22μM。此外,我们通过分子对接和动态(MD)模拟预测了ZMF-005和PAK1的结合模式。另外,据报道ZMF-005在MDA-MB-231细胞中诱导明显的凋亡并抑制迁移。这些发现共同表明ZMF-005 是用于乳腺癌治疗的新型有效PAK1抑制剂。

更新日期:2020-06-29
down
wechat
bug