| http://purl.uniprot.org/citations/36476046 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36476046 | http://www.w3.org/2000/01/rdf-schema#comment | "The non-receptor protein tyrosine phosphatase (PTP) SHP2 encoded by the PTPN11 gene is a critical regulator in a number of cellular signalling processes and pathways, including the MAPK and the immune-inhibitory programmed cell death PD-L1/PD-1 pathway. Hyperactivation and inactivation of SHP2 is of great therapeutic interest for its association with multiple developmental disorders and cancer-related diseases. In this work, we characterised a potent SHP2 allosteric inhibitor 2-((3 R,4R)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-5-(2,3-dichlorophenyl)-3-methylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (PB17-026-01) by using structure-based design. To study the structure-activity relationship, we compared co-crystal structures of SHP2 bound with PB17-026-01 and its analogue compound PB17-036-01, which is ∼20-fold less active than PB17-026-01, revealing that both of the compounds are bound to SHP2 in the allosteric binding pocket and PB17-026-01 forms more polar contacts with its terminal group. Overall, our results provide new insights into the modes of action of allosteric SHP2 inhibitor and a guide for the design of SHP2 allosteric inhibitor."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.org/dc/terms/identifier | "doi:10.1080/14756366.2022.2151594"xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/author | "Liu B."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/author | "Luo Y."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/author | "Li J."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/author | "Liu L."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/author | "Sun M."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/author | "Zheng W."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/author | "Zhu J."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/author | "Zong Y."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/name | "J Enzyme Inhib Med Chem"xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/pages | "398-404"xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/title | "Discovery of the SHP2 allosteric inhibitor 2-((3R,4R)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-5-(2,3-dichlorophenyl)-3-methylpyrrolo[2,1-f][1,2,4] triazin-4(3H)-one."xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://purl.uniprot.org/core/volume | "38"xsd:string |
| http://purl.uniprot.org/citations/36476046 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/36476046 |
| http://purl.uniprot.org/citations/36476046 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/36476046 |
| http://purl.uniprot.org/uniprot/#_Q06124-mappedCitation-36476046 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36476046 |
| http://purl.uniprot.org/uniprot/Q06124 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/36476046 |