2. Academic Validation
  3. Discovery of novel VEGFR-2 inhibitors through virtual screening, synthesis and bioactivity evaluation

Discovery of novel VEGFR-2 inhibitors through virtual screening, synthesis and bioactivity evaluation

  • Bioorg Med Chem Lett. 2025 Oct 3:130423. doi: 10.1016/j.bmcl.2025.130423.
Xi Gu 1,  Linquan Li 2,  Jianquan Yin 3,  Zhili Zuo 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China; School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, UCAS, Hangzhou 310024, China; University of Chinses Academy of Sciences, Beijing 100049, China.
  • 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China; School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, UCAS, Hangzhou 310024, China.
  • 3 Department of Medical Office, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province 310000, China. Electronic address: Yinjianquan123@163.com.
  • 4 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China; School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, UCAS, Hangzhou 310024, China; University of Chinses Academy of Sciences, Beijing 100049, China. Electronic address: zlzuo@ucas.ac.cn.
PMID: 41046919 DOI: 10.1016/j.bmcl.2025.130423
Abstract

Vascular endothelial growth factor receptor 2 (VEGFR-2) is an attractive antitumor target. By effectively inhibiting the overexpression of VEGFR-2, it suppresses the abnormal angiogenesis occurring within tumors. Although some inhibitors targeting VEGFR-2 have been identified, the drug resistance is an unignorable disadvantage to make the urgent need of new structure inhibitors. In this study, an innovative approach involving vast chemical space similarity searching was applied using sunitinib as a template to generate a series of structurally novel and synthetically accessible small molecules. A series robust virtual screening methods were employed to discover promising compounds for synthesis and evaluation of their kinase inhibitory activity against VEGFR-2. The results demonstrated that two of these compounds, GL-3 (IC50 = 5.44 μM) and GL-1 (IC50 = 13.4 μM), exhibited inhibitory activity against VEGFR-2. Subsequently, molecular dynamics simulations were conducted to investigate the interaction mechanisms of these active molecules with VEGFR-2. In summary, this study offers novel perspectives on the development of VEGFR-2 inhibitors and offers an innovative strategy for discovering novel Anticancer drugs.

Keywords

Inhibition evaluation; Similarity searching; Synthesis; VEGFR-2; Vast chemical space.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z