{"doi":"10.1021/acsptsci.3c00010","title":"Biochemical Discovery, Intracellular Evaluation, and Crystallographic Characterization of Synthetic and Natural Product Adenosine 3′,5′-Cyclic Monophosphate-Dependent Protein Kinase A (PKA) Inhibitors","abstract":"The recent demonstration that adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) plays an oncogenic role in a number of important cancers has led to a renaissance in drug development interest targeting this kinase. We therefore have established a suite of biochemical, cell-based, and structural biology assays for identifying and evaluating new pharmacophores for PKA inhibition. This discovery process started with a 384-well high-throughput screen of more than 200,000 substances, including fractionated natural product extracts. Identified active compounds were further prioritized in biochemical, biophysical, and cell-based assays. Priority lead compounds were assessed in detail to fully characterize several previously unrecognized PKA pharmacophores including the generation of new X-ray crystallography structures demonstrating unique interactions between PKA and bound inhibitor molecules.","journal":"ACS Pharmacology & Translational Science","year":2023,"id":372425,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"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":903228,"name":"Ning Li","orcid":"0000-0002-6224-1809","position":1,"is_corresponding":false},{"id":364782,"name":"Juliana A. Martinez Fiesco","orcid":"0000-0002-2396-0974","position":2,"is_corresponding":false},{"id":946722,"name":"Masoumeh Dalilian","orcid":null,"position":3,"is_corresponding":false},{"id":422588,"name":"Dongdong Wang","orcid":"0000-0002-7824-2507","position":4,"is_corresponding":false},{"id":422590,"name":"Emily A. Smith","orcid":"0000-0001-8869-2336","position":5,"is_corresponding":false},{"id":772115,"name":"Antony Wamiru","orcid":null,"position":6,"is_corresponding":false},{"id":366783,"name":"Rohan Shah","orcid":"0000-0003-4796-0394","position":7,"is_corresponding":false},{"id":529136,"name":"Ekaterina I. Goncharova","orcid":null,"position":8,"is_corresponding":false},{"id":445219,"name":"John A. Beutler","orcid":"0000-0002-4646-1924","position":9,"is_corresponding":false},{"id":257551,"name":"Tanja Grkovic","orcid":"0000-0002-6537-3997","position":10,"is_corresponding":false},{"id":486465,"name":"Ping Zhang","orcid":"0000-0002-0340-281X","position":11,"is_corresponding":false},{"id":257552,"name":"Barry R. O’Keefe","orcid":"0000-0003-0772-4856","position":12,"is_corresponding":false},{"id":257548,"name":"Brice A. P. Wilson","orcid":"0000-0001-8988-1964","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:15:54.000926Z","pmid":"37082750","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":[]}