{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mathison CJN"],"funding":["National Institute of General Medical Sciences"],"pagination":["1912-1919"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8667305"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(12)"],"pubmed_abstract":["The selective inhibition of RET kinase as a treatment for relevant cancer types including lung adenocarcinoma has garnered considerable interest in recent years and prompted a variety of efforts toward the discovery of small-molecule therapeutics. Hits uncovered via the analysis of archival kinase data ultimately led to the identification of a promising pyrrolo[2,3-d]pyrimidine scaffold. The optimization of this pyrrolo[2,3-d]pyrimidine core resulted in compound 1, which demonstrated potent in vitro RET kinase inhibition and robust in vivo efficacy in RET-driven tumor xenografts upon multiday dosing in mice. The administration of 1 was well-tolerated at established efficacious doses (10 and 30 mg/kg, po, qd), and plasma exposure levels indicated a "],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["Antitarget Selectivity and Tolerability of Novel Pyrrolo[2,3-d]pyrimidine RET Inhibitors."],"pmcid":["PMC8667305"],"funding_grant_id":["P30 GM124169-01"],"pubmed_authors":["Jiang J","Molteni V","Tellew JE","Chianelli D","Gao MY","Lee C","Rucker PV","Xie YF","Bursulaya B","Kinyamu-Akunda J","Mathison CJN","Nelson J","Shaffer J","Li C","Hua S","Sarkisova Y","Li L","Galkin A","Li N","Yang Y","Kasibhatla S","Huang Z","Kikkawa R","Epple R","Briones S","Roland J"],"additional_accession":[]},"is_claimable":false,"name":"Antitarget Selectivity and Tolerability of Novel Pyrrolo[2,3-d]pyrimidine RET Inhibitors.","description":"The selective inhibition of RET kinase as a treatment for relevant cancer types including lung adenocarcinoma has garnered considerable interest in recent years and prompted a variety of efforts toward the discovery of small-molecule therapeutics. Hits uncovered via the analysis of archival kinase data ultimately led to the identification of a promising pyrrolo[2,3-d]pyrimidine scaffold. The optimization of this pyrrolo[2,3-d]pyrimidine core resulted in compound 1, which demonstrated potent in vitro RET kinase inhibition and robust in vivo efficacy in RET-driven tumor xenografts upon multiday dosing in mice. The administration of 1 was well-tolerated at established efficacious doses (10 and 30 mg/kg, po, qd), and plasma exposure levels indicated a ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Dec","modification":"2025-04-18T20:04:34.185Z","creation":"2025-04-07T07:50:51.499Z"},"accession":"S-EPMC8667305","cross_references":{"pubmed":["34917254"],"doi":["10.1021/acsmedchemlett.1c00450"]}}