title: Synthesis and identification of unprecedented selective inhibitors of CK1ε.
abstract: A small and structure-biased library of enantiopure anti-β-amino alcohols was prepared in a straightforward manner by a simplified version of the Reetz protocol. Antiproliferative activity testing against a panel of five human solid tumor cell lines gave GI50 values in the range 1-20 μM. The reverse screening by computational methods against 58 proteins involved in cancer pointed to kinases as possible therapeutic target candidates. The experimental determination of the interaction with 456 kinases indicated that the compounds behave as selective CK1ε inhibitors. Our results demonstrate that the lead compound represents the first selective CK1ε inhibitor with proven antiproliferative activity in cancer cell lines.
authors.affiliation: Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, C/ Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain.
authors.forename: Gastón
authors.initials: G
authors.lastname: Silveira-Dorta
authors.affiliation: Centro de Química da Madeira, Centro de Ciências Exatas e da Engenharia, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal.
authors.forename: Inês J
authors.initials: IJ
authors.lastname: Sousa
authors.affiliation: Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, C/ Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain; Centro de Química da Madeira, Centro de Ciências Exatas e da Engenharia, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal.
authors.forename: Miguel X
authors.initials: MX
authors.lastname: Fernandes
authors.affiliation: Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, C/ Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Martín
authors.affiliation: Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, C/ Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain. Electronic address: jmpadron@ull.es.
authors.forename: José M
authors.initials: JM
authors.lastname: Padrón
mesh_terms: D000605:Amino Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048149:Casein Kinase 1 epsilon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000605:Amino Alcohols; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D048149:Casein Kinase 1 epsilon
keywords: Antitumor agents; Casein kinase 1 epsilon; Enzyme inhibitors; Sphingoid bases; Target fishing