3754-52-7Relevant articles and documents
A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET
Li, Jing,Tan, Guishan,Cai, Yabo,Liu, Ruihuan,Xiong, Xiaolin,Gu, Baohua,He, Wei,Liu, Bing,Ren, Qingyun,Wu, Jianping,Chi, Bo,Zhang, Hang,Zhao, Yanzhong,Xu, Yangrui,Zou, Zhenxing,Kang, Fenghua,Xu, Kangping
, (2021)
MET, the receptor of hepatocyte growth factor (HGF), is a driving factor in renal cell carcinoma (RCC) and also a proven drug target for cancer treatment. To improve the activity and to investigate the mechanisms of action of Apigenin (APG), novel derivatives of APG with improved properties were synthesized and their activities against Caki-1 human renal cancer cell line were evaluated. It was found that compound 15e exhibited excellent potency against the growth of multiple RCC cell lines including Caki-1, Caki-2 and ACHN and is superior to APG and Crizotinib. Subsequent investigations demonstrated that compound 15e can inhibit Caki-1 cell proliferation, migration and invasion. Mechanistically, 15e directly targeted the MET kinase domain, decreased its auto-phosphorylation at Y1234/Y1235 and inhibited its kinase activity and downstream signaling. Importantly, 15e had inhibitory activity against mutant MET V1238I and Y1248H which were resistant to approved MET inhibitors Cabozantinib, Crizotinib or Capmatinib. In vivo tumor graft study confirmed that 15e repressed RCC growth through inhibition of MET activation. These results indicate that compound 15e has the potential to be developed as a treatment for RCC, and especially against drug-resistant MET mutations.
Synthesis of new biheterocycles by a one-pot sonogashira coupling reaction
Deodhar, Mandar,Black, David Stc.,Kumar, Naresh
, p. 1489 - 1501 (2011/05/14)
Halogenated flavones, isoflavones and indoles were subjected to a one-pot Sonogashira coupling reaction to generate a series of new biheterocyclic compounds. The methodology can be readily adapted to the synthesis of a wide variety of substituted biheterocycles. The Japan Institute of Heterocyclic Chemistry.