{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang L"],"funding":["National Institute of Allergy and Infectious Diseases","NIAID NIH HHS"],"pagination":["1460-1480"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10950204"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(2)"],"pubmed_abstract":["While progress has been made in the effort to eradicate malaria, the disease remains a significant threat to global health. Acquired resistance to frontline treatments is emerging in Africa, urging a need for the development of novel antimalarial agents. Repurposing human kinase inhibitors provides a potential expedited route given the availability of a diverse array of kinase-targeting drugs that are approved or in clinical trials. Phenotypic screening of a library of type II human kinase inhibitors identified compound <b>1</b> as a lead antimalarial, which was initially developed to target human ephrin type A receptor 2 (EphA2). Here, we report a structure-activity relationship study and lead optimization of compound <b>1</b>, which led to compound <b>33,</b> with improved antimalarial activity and selectivity."],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Discovery of Potent Antimalarial Type II Kinase Inhibitors with Selectivity over Human Kinases."],"pmcid":["PMC10950204"],"funding_grant_id":["AI172066","R01 AI152533","R01 AI169892","R01 AI172066"],"pubmed_authors":["Calla J","Nardella F","Rocamora F","Laureano De Souza M","Charlton JT","Bohmer MJ","Wang J","Chakrabarti D","Wang L","Gray NS","Schindler KA","Cooper RA","Montejo L","Treat M","Winzeler EA","Chakrabarti R","Mittal N","Tumwebaze PK","Rosenthal PJ"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of Potent Antimalarial Type II Kinase Inhibitors with Selectivity over Human Kinases.","description":"While progress has been made in the effort to eradicate malaria, the disease remains a significant threat to global health. Acquired resistance to frontline treatments is emerging in Africa, urging a need for the development of novel antimalarial agents. Repurposing human kinase inhibitors provides a potential expedited route given the availability of a diverse array of kinase-targeting drugs that are approved or in clinical trials. Phenotypic screening of a library of type II human kinase inhibitors identified compound <b>1</b> as a lead antimalarial, which was initially developed to target human ephrin type A receptor 2 (EphA2). Here, we report a structure-activity relationship study and lead optimization of compound <b>1</b>, which led to compound <b>33,</b> with improved antimalarial activity and selectivity.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jan","modification":"2025-04-04T02:09:19.458Z","creation":"2025-04-04T02:09:19.458Z"},"accession":"S-EPMC10950204","cross_references":{"pubmed":["38214254"],"doi":["10.1021/acs.jmedchem.3c02046"]}}