98895-60-4Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of quinazoline derivatives with covalent reversible warheads as potential FGFR4 inhibitors
Che, Jinxin,Dong, Xiaowu,Du, Jiaming,Gao, Jian,He, Qiaojun,Lu, Yang,Luo, Mengxin,Luo, Peihua,Nie, Wenwen,Pan, Chenghao,Wang, Jiao,Zhu, Hong
, (2022/03/16)
Fibroblast growth factor receptor 4 (FGFR4) together with co-receptors modulate the activation of downstream proteins that regulate fundamental processes, and elevated FGFR4 activity is associated with Hepatocellular Carcinoma (HCC). Hence, FGFR4 is a promising therapeutic target for HCC. Based on BLU9931, we designed and synthesized a series of phenylquinazoline derivatives as novel inhibitors of FGFR4 through the covalent reversible strategy. Among them, a novel compound (C3) showed FGFR4 and cell proliferation inhibitory activity. Cellular mechanism studies demonstrated that compound C3 induced apoptosis via the FGFR4 signaling pathway blockage. Further mechanism study showed that C3 has the reversible covalent binding capacity, could be used as a reference for the development of novel FGFR4 covalent reversible inhibitors.
Efficient targeted oncogenic KRASG12C degradation via first reversible-covalent PROTAC
Liu, Tongzheng,Lu, Xiaoyun,Wang, Chaofan,Wen, Yalei,Yang, Fang,Zhang, Zhi-Min,Zhou, Yang,Zhou, Yuee
, (2022/01/11)
KRAS is the most frequently mutated oncogene and plays a predominant role in driving initiation and progression of multiple cancers. Attempts to degrade the oncogene KRASG12C with PROTAC strategy have been considered as an alternative strategy to combate cancers. However, the irreversible PROTACs may compromise the substoichiometric activity to decrease the potency. Herein, we report the development of YF135, the first reversible-covalent PROTAC capable of recruiting VHL mediated proteasomal degradation of KRASG12C. YF135 induces the rapid and sustained degradation of endogenous KRASG12C and attenuates pERK signaling in H358 and H23 cells in a reversible manner.
Structure-based design and synthesis of covalent-reversible inhibitors to overcome drug resistance in EGFR
Basu, Debjit,Richters, André,Rauh, Daniel
, p. 2767 - 2780 (2015/06/08)
The clinical success of covalent kinase inhibitors in the treatment of EGFR-dependent non-small cell lung cancer (NSCLC) has rejuvenated the appreciation of reactive small molecules. Acquired drug resistance against first-line EGFR inhibitors remains the
