{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lu X"],"funding":["Government of Guangdong Province","Guangzhou City Key Laboratory of Precision Chemical Drug Development, Jinan University","Jinan University","Natural Science Foundation of Guangdong Province","National Natural Science Foundation of China","Institutes for Drug Discovery and Development, Chinese Academy of Science"],"pagination":["1123-1127"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6231186"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(11)"],"pubmed_abstract":["EGFR<sup>C797S</sup> mutation inducing resistance against third generation EGFR inhibitor drugs is an emerging \"unmet clinical need\" for nonsmall cell lung cancer patients. The pyrimidopyrimidinone derivative JND3229 was identified as a new highly potent EGFR<sup>C797S</sup> inhibitor with single digit nM potency. It also exhibited good in vitro and in vivo monodrug anticancer efficacy in a xenograft mouse model of BaF3/EGFR<sup>19D/T790M/C797S</sup> cells. A high-resolution X-ray crystallographic structure was also determined to elucidate the interactions between JND3229 and EGFR<sup>T790M/C797S</sup>. Our study provides an important structural and chemical basis for future development of new generation EGFR<sup>C797S</sup> inhibitors as anticancer drugs."],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["Discovery of JND3229 as a New EGFR<sup>C797S</sup> Mutant Inhibitor with In Vivo Monodrug Efficacy."],"pmcid":["PMC6231186"],"funding_grant_id":["31270769","2015A030306042","81673285","21572230","21702075","81425021","CASIMM0120185006","201805010007","2105A030312014"],"pubmed_authors":["Lu X","Tong L","Hu X","Xun Q","Ding J","Sun Y","Ding K","Yun CH","Li Y","Zhang T","Zhu SJ","Xie H","Chen Y","Su Y","Chan S"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of JND3229 as a New EGFR<sup>C797S</sup> Mutant Inhibitor with In Vivo Monodrug Efficacy.","description":"EGFR<sup>C797S</sup> mutation inducing resistance against third generation EGFR inhibitor drugs is an emerging \"unmet clinical need\" for nonsmall cell lung cancer patients. The pyrimidopyrimidinone derivative JND3229 was identified as a new highly potent EGFR<sup>C797S</sup> inhibitor with single digit nM potency. It also exhibited good in vitro and in vivo monodrug anticancer efficacy in a xenograft mouse model of BaF3/EGFR<sup>19D/T790M/C797S</sup> cells. A high-resolution X-ray crystallographic structure was also determined to elucidate the interactions between JND3229 and EGFR<sup>T790M/C797S</sup>. Our study provides an important structural and chemical basis for future development of new generation EGFR<sup>C797S</sup> inhibitors as anticancer drugs.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Nov","modification":"2026-05-06T03:42:52.543Z","creation":"2019-11-15T08:03:51Z"},"accession":"S-EPMC6231186","cross_references":{"pubmed":["30429956"],"doi":["10.1021/acsmedchemlett.8b00373"]}}