{"doi":"10.1101/2022.12.15.520623","title":"SGC-CLK-1 (CAF-170) a chemical probe for the Cdc2-Like kinases CLK1, CLK2, and CLK4","abstract":"Abstract Small molecule modulators are important tools to study both basic biology and the complex signaling of protein kinases. The cdc2-like kinases (CLK) are a family of four kinases that have garnered recent interest for their involvement in a diverse set of diseases such as neurodegeneration, autoimmunity, and many cancers. Targeted medicinal chemistry around a CLK inhibitor hit identified through screening of a kinase inhibitor set against a large panel of kinases allowed us to identify a potent and selective inhibitor of CLK1, 2 and 4. Here, we present the synthesis, selectivity, and potential binding site of this compound – SGC-CLK-1. We further show CLK2 has the highest binding affinity, and high CLK2 expression correlates with a lower IC 50 in a screen of multiple cancer cell lines. Finally, we show that SGC-CLK-1 not only reduces serine arginine rich (SR) protein phosphorylation, but also alters SR protein and CLK2 subcellular localization in a reversible way. Therefore, we anticipate that this compound will be a valuable tool for increasing our understanding of CLKs and their targets, SR proteins, at the level of phosphorylation and subcellular localization.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313717,"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":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273786,"name":"Carrow I. Wells","orcid":"0000-0003-4799-6792","position":1,"is_corresponding":false},{"id":634699,"name":"Martin Schröder","orcid":"0000-0001-7631-7766","position":2,"is_corresponding":false},{"id":499156,"name":"Xiao Song","orcid":"0000-0002-3171-4300","position":3,"is_corresponding":false},{"id":1012807,"name":"Carla Alamillo-Ferrer","orcid":null,"position":4,"is_corresponding":false},{"id":626611,"name":"Anshika Goenka","orcid":"0000-0003-2807-2551","position":5,"is_corresponding":false},{"id":885568,"name":"Rebeca Piatniczka Iglesia","orcid":"0000-0002-5852-2632","position":6,"is_corresponding":false},{"id":885569,"name":"Minghui Lu","orcid":"0000-0002-7863-5255","position":7,"is_corresponding":false},{"id":263142,"name":"Bo Hu","orcid":"0000-0002-9882-4053","position":8,"is_corresponding":false},{"id":491126,"name":"Frank E. Kwarcinski","orcid":null,"position":9,"is_corresponding":false},{"id":1012808,"name":"Parvathi Sintha","orcid":null,"position":10,"is_corresponding":false},{"id":490039,"name":"Chandi de Silva","orcid":"0000-0001-6197-0201","position":11,"is_corresponding":false},{"id":688345,"name":"Mohammad Anwar Hossain","orcid":"0000-0001-8684-8755","position":12,"is_corresponding":false},{"id":490037,"name":"Alfredo Picado","orcid":"0000-0002-8397-3312","position":13,"is_corresponding":false},{"id":344688,"name":"William J. Zuercher","orcid":"0000-0002-9836-0068","position":14,"is_corresponding":false},{"id":490040,"name":"Reena Zutshi","orcid":"0000-0002-2582-1484","position":15,"is_corresponding":false},{"id":239988,"name":"Stefan Knapp","orcid":"0000-0001-5995-6494","position":16,"is_corresponding":false},{"id":319601,"name":"Rebecca B. Riggins","orcid":"0000-0002-1555-4431","position":17,"is_corresponding":false},{"id":49204,"name":"Shi-Yuan Cheng","orcid":"0000-0003-1737-0588","position":18,"is_corresponding":false},{"id":273790,"name":"David H. Drewry","orcid":"0000-0001-5973-5798","position":19,"is_corresponding":false},{"id":626612,"name":"Deanna Tiek","orcid":"0000-0002-2881-7691","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T00:33:48.490749Z","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":[]}