1821666-85-6Relevant articles and documents
WDR5-MYC INHIBITORS
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Paragraph 0099; 00122; 00124; 00132-00133, (2021/05/29)
Substituted N-heteroaryl sulfonamide compounds inhibit WDR5-MYC interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject such as cancer cell proliferation.
Structure-Based Design of 6-Chloro-4-aminoquinazoline-2-carboxamide Derivatives as Potent and Selective p21-Activated Kinase 4 (PAK4) Inhibitors
Hao, Chenzhou,Zhao, Fan,Song, Hongyan,Guo, Jing,Li, Xiaodong,Jiang, Xiaolin,Huan, Ran,Song, Shuai,Zhang, Qiaoling,Wang, Ruifeng,Wang, Kai,Pang, Yu,Liu, Tongchao,Lu, Tianqi,Huang, Wanxu,Wang, Jian,Lin, Bin,He, Zhonggui,Li, Haitao,Li, Feng,Zhao, Dongmei,Cheng, Maosheng
, p. 265 - 285 (2018/02/10)
Herein, we report the discovery and characterization of a novel class of PAK4 inhibitors with a quinazoline scaffold. Based on the shape and chemical composition of the ATP-binding pocket of PAKs, we chose a 2,4-diaminoquinazoline series of inhibitors as a starting point. Guided by X-ray crystallography and a structure-based drug design (SBDD) approach, a series of novel 4-aminoquinazoline-2-carboxamide PAK4 inhibitors were designed and synthesized. The inhibitors' selectivity, therapeutic potency, and pharmaceutical properties were optimized. One of the best compounds, 31 (CZh226), showed remarkable PAK4 selectivity (346-fold vs PAK1) and favorable kinase selectivity profile. Moreover, this compound potently inhibited the migration and invasion of A549 tumor cells by regulating the PAK4-directed downstream signaling pathways in vitro. Taken together, these data support the further development of 31 as a lead compound for PAK4-targeted anticancer drug discovery and as a valuable research probe for the further biological investigation of group II PAKs.
