Discovery of 6-[(3
| Autor: | Barbara, Czako, Yuting, Sun, Timothy, McAfoos, Jason B, Cross, Paul G, Leonard, Jason P, Burke, Christopher L, Carroll, Ningping, Feng, Angela L, Harris, Yongying, Jiang, Zhijun, Kang, Jeffrey J, Kovacs, Pijus, Mandal, Brooke A, Meyers, Faika, Mseeh, Connor A, Parker, Simon S, Yu, Christopher C, Williams, Qi, Wu, Maria Emilia, Di Francesco, Giulio, Draetta, Timothy, Heffernan, Joseph R, Marszalek, Nancy E, Kohl, Philip, Jones |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Dose-Response Relationship
Drug Molecular Structure Administration Oral Antineoplastic Agents Protein Tyrosine Phosphatase Non-Receptor Type 11 Neoplasms Experimental Mice Structure-Activity Relationship Cell Line Tumor Drug Discovery Animals Humans Drug Screening Assays Antitumor Enzyme Inhibitors Cell Proliferation |
| Zdroj: | Journal of medicinal chemistry. 64(20) |
| ISSN: | 1520-4804 |
| Popis: | Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) plays a role in receptor tyrosine kinase (RTK), neurofibromin-1 (NF-1), and Kirsten rat sarcoma virus (KRAS) mutant-driven cancers, as well as in RTK-mediated resistance, making the identification of small-molecule therapeutics that interfere with its function of high interest. Our quest to identify potent, orally bioavailable, and safe SHP2 inhibitors led to the discovery of a promising series of pyrazolopyrimidinones that displayed excellent potency but had a suboptimal |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|