{"doi":"10.1016/j.bmc.2020.115962","title":"Discovery of DB18, a potent inhibitor of CLK kinases with a high selectivity against DYRK1A kinase","abstract":null,"journal":"Bioorganic &amp; Medicinal Chemistry","year":2021,"id":605919,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1555254,"name":"Anagani Kanaka Durga Bhavani","orcid":null,"position":1,"is_corresponding":false},{"id":1555255,"name":"Pasula Aparna","orcid":null,"position":2,"is_corresponding":false},{"id":1555256,"name":"Nangunoori Sampath Kumar","orcid":null,"position":3,"is_corresponding":false},{"id":1555257,"name":"Hélène Solhi","orcid":null,"position":4,"is_corresponding":false},{"id":1555258,"name":"Rémy Le Guevel","orcid":null,"position":5,"is_corresponding":false},{"id":1405023,"name":"Blandine Baratte","orcid":"0000-0002-2064-9558","position":6,"is_corresponding":false},{"id":202284,"name":"Sandrine Ruchaud","orcid":null,"position":7,"is_corresponding":false},{"id":1405027,"name":"Stéphane Bach","orcid":"0000-0002-7186-7483","position":8,"is_corresponding":false},{"id":1555259,"name":"Surender Singh Jadav","orcid":"0000-0002-5397-8956","position":9,"is_corresponding":false},{"id":1555260,"name":"Chada Raji Reddy","orcid":null,"position":10,"is_corresponding":false},{"id":165097,"name":"Thierry Roisnel","orcid":null,"position":11,"is_corresponding":false},{"id":1555261,"name":"Paul Mosset","orcid":null,"position":12,"is_corresponding":false},{"id":1555262,"name":"Nicolas Levoin","orcid":null,"position":13,"is_corresponding":false},{"id":1555263,"name":"René Grée","orcid":null,"position":14,"is_corresponding":false},{"id":1555253,"name":"Dabbugoddu Brahmaiah","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Discovery of DB18, a potent inhibitor of CLK kinases with a high selectivity against DYRK1A kinase","abstract":"We describe in this paper the synthesis of a novel series of anilino-2-quinazoline derivatives. These compounds have been screened against a panel of eight mammalian kinases and in parallel they were tested for cytotoxicity on a representative panel of seven cancer cell lines. One of them (DB18) has been found to be a very potent inhibitor of human \"CDC2-like kinases\" CLK1, CLK2 and CLK4, with IC<sub>50</sub> values in the 10-30 nM range. Interestingly, this molecule is inactive at 100 μM on the closely related \"dual-specificity tyrosine-regulated kinase 1A\" (DYRK1A). Extensive molecular simulation studies have been performed on the relevant kinases to explain the strong affinity of this molecule on CLKs, as well as its selectivity against DYRK1A.","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33422908","pmcid":null,"openalex_id":"https://openalex.org/W3116389162","authors":[],"funders":[],"total_grants":0,"fwci":0.8988,"citation_percentile":0.74308979,"influential_citations":0,"citation_trend":[{"year":2021,"count":2},{"year":2022,"count":2},{"year":2023,"count":4},{"year":2024,"count":6},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"green","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://doi.org/10.7270/q2kd22js","host_type":"repository"},{"url":"https://doi.org/10.7270/q2kd22js","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S0968089620307926?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0968089620307926?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bmc.2020.115962","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33422908","host_type":"repository"},{"url":"https://hal.science/hal-03128547","host_type":"repository"},{"url":"https://hal.archives-ouvertes.fr/hal-03864229","host_type":"repository"}],"fields_of_study":["Chronic Lymphocytic Leukemia Research","Chronic Myeloid Leukemia Treatments","Quinazolinone synthesis and applications"],"mesh_terms":["Dyrk Kinases","Antineoplastic Agents","Cell Survival","Dose-Response Relationship, Drug","Drug Screening Assays, Antitumor","Humans","Protein-Tyrosine Kinases","Structure-Activity Relationship","Molecular Structure","Protein Serine-Threonine Kinases","Cell Line, Tumor","Protein Kinase Inhibitors","Cell Proliferation","Drug Discovery"],"keywords":["DYRK1A","Kinase","Chemistry","Quinazoline","Protein-Serine-Threonine Kinases","Small molecule","Selectivity","Tyrosine kinase","Biochemistry","Cyclin-dependent kinase 1","Structure–activity relationship","Stereochemistry","In vitro","Cell cycle","Protein kinase A","Cell","Signal transduction","Kinases","Cancer","Molecular modelling","Triazoles","Quinazolines"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T03:31:18.554564Z","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":[]}