Discovery of 6-[(3
Administration, Oral
Animals
Antineoplastic Agents
/ administration & dosage
Cell Line, Tumor
Cell Proliferation
/ drug effects
Dose-Response Relationship, Drug
Drug Discovery
Drug Screening Assays, Antitumor
Enzyme Inhibitors
/ administration & dosage
Humans
Mice
Molecular Structure
Neoplasms, Experimental
/ drug therapy
Protein Tyrosine Phosphatase, Non-Receptor Type 11
/ antagonists & inhibitors
Structure-Activity Relationship
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
28 10 2021
28 10 2021
Historique:
pubmed:
14
10
2021
medline:
15
12
2021
entrez:
13
10
2021
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 34643390
doi: 10.1021/acs.jmedchem.1c01132
doi:
Substances chimiques
Antineoplastic Agents
0
Enzyme Inhibitors
0
PTPN11 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 11
EC 3.1.3.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM