克拉斯
胰腺癌
癌症研究
GTP'
癌症
孟鲁卡斯特
癌细胞
药理学
生物
化学
医学
内科学
结直肠癌
生物化学
酶
哮喘
作者
Yannan Xia,Shujie Zhang,Hongyi Luo,Yumeng Wang,Yuanyuan Jiang,Jingwei Jiang,Shengtao Yuan
标识
DOI:10.1016/j.ejphar.2023.176157
摘要
Pancreatic cancer is one of the most lethal cancer types with 5-year survival rate of ∼10.8%. Various KRAS mutations exist in ∼85% pancreatic cancer cell lines. Mutated KRAS is a major cause that leads cancer cell proliferation. Chemotherapy is still the major treatment for pancreatic cancer. Alternatively, repositioning old drug to inhibit mutated KRAS may be a cost-effective way for pancreatic cancer treatment. In this study, we choose mutated KRAS (G12D) as a target. Based on mutated KRAS GTP binding domain (hydrolyze GTP to GDP), we perform virtual screening on FDA-approved drugs. Montelukast shows strong binding affinity to mutated KRAS as well as interfering both GTP and GDP binding to mutated KRAS. Furthermore, Montelukast shows very strong anti-proliferation effect on mutated KRAS pancreatic cancer cells both in vitro and in vivo. Our results support repositioning of Montelukast as single agent for pancreatic cancer treatment.
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