135065-69-9Relevant articles and documents
HPK1 ANTAGONISTS AND USES THEREOF
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Paragraph 0836; 0837, (2021/03/19)
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of HPK1, and the treatment of HPK1-mediated disorders.
Development of the First Generation of Disulfide-Based Subtype-Selective and Potent Covalent Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors
Liu, Yifu,Xie, Zuoquan,Zhao, Dan,Zhu, Jin,Mao, Fei,Tang, Shuai,Xu, Hui,Luo, Cheng,Geng, Meiyu,Huang, Min,Li, Jian
, p. 2227 - 2244 (2017/04/03)
Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and are responsible for aberrant glucose metabolism. We previously described bis(4-morpholinyl thiocarbonyl)-disulfide (JX06, 16) as the first covalent inhibitor of PDK1. Here, on the basis of the scaffold of 16, we identify two novel types of disulfide-based PDK1 inhibitors. The most potent analogue, 3a, effectively inhibits PDK1 both at the molecular (kinact/Ki = 4.17 × 103 M-1 s-1) and the cellular level (down to 0.1 μM). In contrast to 16, 3a is a potent and subtype-selective inhibitor of PDK1 with >40-fold selectivity for PDK2-4. 3a also significantly alters glucose metabolic pathways in A549 cells by decreasing ECAR and increasing ROS. Moreover, in the xenograft models, 3a shows significant antitumor activity with no negative effect to the mice weight. Collectively, these data demonstrate that 3a may be an excellent lead compound for the treatment of cancer as a first-generation subtype-selective and covalent PDK1 inhibitor.
4-Substituted quinazoline derivatives as novel EphA2 receptor tyrosine kinase inhibitors
Lim, Chae Jo,Oh, Kwang-Seok,Ha, Jae Du,Lee, Jeong Hyun,Seo, Ho Won,Chae, Chong Hack,Kim, Dae-Ghon,Lee, Mi-Jin,Lee, Byung Ho
, p. 4080 - 4083 (2014/09/29)
Erythropoietin-producing hepatocellular receptor tyrosine kinase subtype A2 (EphA2) is an attractive therapeutic target for suppressing tumor progression. In our efforts to discover novel small molecules to inhibit EphA2, a class of compound based on 4-substituted quinazoline containing 7-(morpholin-2-ylmethoxy) group was identified as a novel hit by high throughput screening campaign. Structural modification of parent quinazoline scaffolds by introducing substituents on aniline displayed potent inhibitory activities toward EphA2.