{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["14(2)"],"submitter":["Torrente E"],"funding":["Collezione Nazionale di Composti Chimici e Centro di screening"],"pubmed_abstract":["Protein tyrosine phosphatase SHP2 is an oncogenic protein that can regulate different cytokine receptor and receptor tyrosine kinase signaling pathways. We report here the identification of a novel series of SHP2 allosteric inhibitors having an imidazopyrazine 6,5-fused heterocyclic system as the central scaffold that displays good potency in enzymatic and cellular assays. SAR studies led to the identification of compound <b>8</b>, a highly potent SHP2 allosteric inhibitor. X-ray studies showed novel stabilizing interactions with respect to known SHP2 inhibitors. Subsequent optimization allowed us to identify analogue <b>10</b>, which possesses excellent potency and a promising PK profile in rodents."],"journal":["ACS medicinal chemistry letters"],"pagination":["156-162"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9923835"],"repository":["biostudies-literature"],"pubmed_title":["Discovery of a Novel Series of Imidazopyrazine Derivatives as Potent SHP2 Allosteric Inhibitors."],"pmcid":["PMC9923835"],"pubmed_authors":["Fodale V","Amaudrut J","Pucci V","Alli C","Ciammaichella A","Ferrigno F","Missineo A","Bisbocci M","Esposito S","Ponzi S","Rossetti I","di Marco A","Toniatti C","Palombo S","Torrente E","Nibbio M","Cellucci A","Sferrazza A","Ontoria JM","Cerretani M","Petrocchi A"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of a Novel Series of Imidazopyrazine Derivatives as Potent SHP2 Allosteric Inhibitors.","description":"Protein tyrosine phosphatase SHP2 is an oncogenic protein that can regulate different cytokine receptor and receptor tyrosine kinase signaling pathways. We report here the identification of a novel series of SHP2 allosteric inhibitors having an imidazopyrazine 6,5-fused heterocyclic system as the central scaffold that displays good potency in enzymatic and cellular assays. SAR studies led to the identification of compound <b>8</b>, a highly potent SHP2 allosteric inhibitor. X-ray studies showed novel stabilizing interactions with respect to known SHP2 inhibitors. Subsequent optimization allowed us to identify analogue <b>10</b>, which possesses excellent potency and a promising PK profile in rodents.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-05-28T21:47:54.285Z","creation":"2025-04-05T14:48:14.204Z"},"accession":"S-EPMC9923835","cross_references":{"pubmed":["36793438"],"doi":["10.1021/acsmedchemlett.2c00454"]}}