211245-62-4Relevant articles and documents
4-substituted pyrido [2, 3-d] pyrimidine-7-ketone compound as well as preparation method and application thereof
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Paragraph 0041-0045, (2021/05/29)
The invention discloses 4-substituted pyrido [2, 3-d] pyrimidine-7-ketone compounds with different general formula structures and pharmaceutically acceptable salts, solvates, polymorphic substances, tautomers, metabolites or prodrugs of the 4-substituted pyrido [2, 3-d] pyrimidine-7-ketone compounds. The invention also discloses an effect of the compound as an NEDD8 activating enzyme inhibitor and an application of the compound in preparation of drugs for treating diseases related to NEDD8 activating enzyme abnormality. Pharmacological results show that the compound has good NEDD8 inhibitory activity, tumor cell proliferation resistance and tumor cell apoptosis promotion effects.
Generating Selective Leads for Mer Kinase Inhibitors-Example of a Comprehensive Lead-Generation Strategy
Nissink, J. Willem M.,Bazzaz, Sana,Blackett, Carolyn,Clark, Matthew A.,Collingwood, Olga,Disch, Jeremy S.,Gikunju, Diana,Goldberg, Kristin,Guilinger, John P.,Hardaker, Elizabeth,Hennessy, Edward J.,Jetson, Rachael,Keefe, Anthony D.,McCoull, William,McMurray, Lindsay,Olszewski, Allison,Overman, Ross,Pflug, Alexander,Preston, Marian,Rawlins, Philip B.,Rivers, Emma,Schimpl, Marianne,Smith, Paul,Truman, Caroline,Underwood, Elizabeth,Warwicker, Juli,Winter-Holt, Jon,Woodcock, Simon,Zhang, Ying
, p. 3165 - 3184 (2021/04/06)
Mer is a member of the TAM (Tyro3, Axl, Mer) kinase family that has been associated with cancer progression, metastasis, and drug resistance. Their essential function in immune homeostasis has prompted an interest in their role as modulators of antitumor immune response in the tumor microenvironment. Here we illustrate the outcomes of an extensive lead-generation campaign for identification of Mer inhibitors, focusing on the results from concurrent, orthogonal high-throughput screening approaches. Data mining, HT (high-throughput), and DECL (DNA-encoded chemical library) screens offered means to evaluate large numbers of compounds. We discuss campaign strategy and screening outcomes, and exemplify series resulting from prioritization of hits that were identified. Concurrent execution of HT and DECL screening successfully yielded a large number of potent, selective, and novel starting points, covering a range of selectivity profiles across the TAM family members and modes of kinase binding, and offered excellent start points for lead development.
PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONES AS CDK INHIBITORS
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Page/Page column 41; 51; 53, (2021/09/17)
The pyrido[2,3-d]pyrimidin-7(8H)-ones of Formula (1) and pharmaceutical compositions containing compounds of Formula (1) as CDK inhibitors are disclosed herein. Methods and use of a compound of Formula 1 in the treatment of cancer and manufacture are also disclosed.
