{"doi":"10.1101/2021.08.24.457553","title":"Discovery of novel potent, cell-permeable inhibitors of <i>P. falciparum</i> cGMP-dependent protein kinase","abstract":"ABSTRACT The discovery of new targets for treatment of malaria advanced with the demonstration that orally administered inhibitors of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) could clear infection in a murine model. This enthusiasm was tempered by unsatisfactory safety and/or pharmacokinetic issues found with these chemotypes. To address the urgent need for new scaffolds, we recently reported the discovery and optimization of novel, potent isoxazole-based PfPKG inhibitors that lacked any obvious safety warnings. This manuscript presents representative in vitro ADME, hERG characterization and cell-based antiparasitic activity of these PfPKG inhibitors. We also report the discovery and structure-activity relationships of a new series with good potency, low hERG activity and cell-based anti-parasitic activity comparable to a literature standard.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226195,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":829678,"name":"Mariana Lozano Gonzalez","orcid":null,"position":1,"is_corresponding":false},{"id":829679,"name":"Shams Ul Mahmood","orcid":null,"position":2,"is_corresponding":false},{"id":583517,"name":"Tyler Eck","orcid":"0000-0003-2464-8138","position":3,"is_corresponding":false},{"id":827989,"name":"Tamara Kreiss","orcid":"0000-0003-1482-5129","position":4,"is_corresponding":false},{"id":827988,"name":"Mariana Laureano de Souza","orcid":"0000-0003-1886-3878","position":5,"is_corresponding":false},{"id":681892,"name":"Samantha O. Aylor","orcid":"0000-0002-8974-3665","position":6,"is_corresponding":false},{"id":398223,"name":"Alison Roth","orcid":"0000-0001-6917-3485","position":7,"is_corresponding":false},{"id":681894,"name":"Patricia Lee","orcid":"0000-0002-8593-2733","position":8,"is_corresponding":false},{"id":697686,"name":"Brandon Pybus","orcid":"0000-0002-0392-225X","position":9,"is_corresponding":false},{"id":389130,"name":"Purnima Bhanot","orcid":"0000-0001-5116-6973","position":10,"is_corresponding":false},{"id":829680,"name":"Dennis Colussi","orcid":null,"position":11,"is_corresponding":false},{"id":721033,"name":"Wayne E. Childers","orcid":"0000-0003-0527-3684","position":12,"is_corresponding":false},{"id":721031,"name":"John Gordon","orcid":"0000-0001-8191-2156","position":13,"is_corresponding":false},{"id":718073,"name":"John J. Siekierka","orcid":"0000-0002-0269-0960","position":14,"is_corresponding":false},{"id":718072,"name":"David P. Rotella","orcid":"0000-0002-8224-218X","position":15,"is_corresponding":false},{"id":828329,"name":"Rammohan R. Yadav Bheemanaboina","orcid":null,"position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-18T23:54:34.185847Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}