{"doi":"10.1021/acsinfecdis.2c00527","title":"Fast-Killing Tyrosine Amide (( <i>S</i> )-SW228703) with Blood- and Liver-Stage Antimalarial Activity Associated with the Cyclic Amine Resistance Locus ( <i>Pf</i> CARL)","abstract":"Current malaria treatments are threatened by drug resistance, and new drugs are urgently needed. In a phenotypic screen for new antimalarials, we identified ( S )-SW228703 (( S )-SW703), a tyrosine amide with asexual blood and liver stage activity and a fast-killing profile. Resistance to ( S )-SW703 is associated with mutations in the Plasmodium falciparum cyclic amine resistance locus ( Pf CARL) and P. falciparum acetyl CoA transporter ( Pf ACT), similarly to several other compounds that share features such as fast activity and liver-stage activity. Compounds with these resistance mechanisms are thought to act in the ER, though their targets are unknown. The tyramine of ( S )-SW703 is shared with some reported Pf CARL-associated compounds; however, we observed that strict S-stereochemistry was required for the activity of ( S )-SW703, suggesting differences in the mechanism of action or binding mode. ( S )-SW703 provides a new chemical series with broad activity for multiple life-cycle stages and a fast-killing mechanism of action, available for lead optimization to generate new treatments for malaria.","journal":"ACS Infectious Diseases","year":2023,"id":359026,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":679740,"name":"Aloysus K. Lawong","orcid":"0000-0002-3367-4883","position":1,"is_corresponding":false},{"id":369677,"name":"Suraksha Gahalawat","orcid":"0000-0002-8004-0322","position":2,"is_corresponding":false},{"id":813317,"name":"Ashwani Kumar","orcid":"0000-0002-2449-9331","position":3,"is_corresponding":false},{"id":240348,"name":"Chao Xing","orcid":"0000-0002-1838-0502","position":4,"is_corresponding":false},{"id":288349,"name":"Nimisha Mittal","orcid":"0000-0002-4810-9334","position":5,"is_corresponding":false},{"id":471520,"name":"Sergio Wittlin","orcid":"0000-0002-0811-0912","position":6,"is_corresponding":false},{"id":870846,"name":"Alisje Churchyard","orcid":"0000-0002-4726-6397","position":7,"is_corresponding":false},{"id":370527,"name":"Hanspeter Niederstrasser","orcid":null,"position":8,"is_corresponding":false},{"id":885826,"name":"Benigno Crespo-Fernández","orcid":"0000-0002-5071-5819","position":9,"is_corresponding":false},{"id":350017,"name":"Bruce A. Posner","orcid":"0000-0002-7033-4933","position":10,"is_corresponding":false},{"id":559331,"name":"Francisco‐Javier Gamo","orcid":"0000-0002-1854-2882","position":11,"is_corresponding":false},{"id":582660,"name":"Jake Baum","orcid":"0000-0002-0275-352X","position":12,"is_corresponding":false},{"id":79127,"name":"Elizabeth A. Winzeler","orcid":"0000-0002-4049-2113","position":13,"is_corresponding":false},{"id":679744,"name":"Benoı̂t Laleu","orcid":"0000-0002-7530-2113","position":14,"is_corresponding":false},{"id":369682,"name":"Joseph M. Ready","orcid":"0000-0003-1305-9581","position":15,"is_corresponding":false},{"id":421934,"name":"Margaret A. Phillips","orcid":"0000-0001-5250-5578","position":16,"is_corresponding":false},{"id":706684,"name":"Leah S. Imlay","orcid":"0000-0001-6048-4615","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:13:48.379546Z","pmid":"36763526","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":[]}