{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:45:34Z","timestamp":1791067534406,"version":"4.1.0"},"reference-count":49,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2015,3,4]],"date-time":"2015-03-04T00:00:00Z","timestamp":1425427200000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons in cortex, brain stem, and spinal cord die progressively, resulting in muscle wasting, paralysis, and death. Currently, effective therapies for ALS are lacking; however, identification of pathological TAR DNA-binding protein 43 (TDP-43) as the hallmark lesion in sporadic ALS suggests new therapeutic targets for pharmacological intervention. Pathological TDP-43 phosphorylation appears to drive the onset and progression of ALS and may result from upregulation of the protein kinase CK-1 in affected neurons, resulting in postranslational TDP-43 modification. Consequently, brain penetrant specific CK-1 inhibitors may provide a new therapeutic strategy for treating ALS and other TDP-43 proteinopathies. Using a chemical genetic approach, we report the discovery and further optimization of a number of potent CK-1\u03b4 inhibitors. Moreover, these small heterocyclic molecules are able to prevent TDP-43 phosphorylation in cell cultures, to increase Drosophila lifespan by reduction of TDP-43 neurotoxicity, and are predicted to cross the blood\u2013brain barrier. Thus, N-(benzothiazolyl)-2-phenyl-acetamides are valuable drug candidates for further studies and may be a new therapeutic approach for ALS and others pathologies in which TDP-43 is involved.<\/jats:p>","DOI":"10.1021\/jm500065f","type":"journal-article","created":{"date-parts":[[2014,3,4]],"date-time":"2014-03-04T10:18:44Z","timestamp":1393928324000},"page":"2755-2772","source":"Crossref","is-referenced-by-count":116,"title":["Protein Kinase CK-1\nInhibitors As New Potential\nDrugs for Amyotrophic Lateral Sclerosis"],"prefix":"10.1021","volume":"57","author":[{"given":"Irene G.","family":"Salado","sequence":"first","affiliation":[{"name":"CSIC , , Juan de la Cierva 3 , ,","place":["Madrid, Spain, 28006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Redondo","sequence":"additional","affiliation":[{"name":"CSIC , , Juan de la Cierva 3 , ,","place":["Madrid, Spain, 28006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murilo L.","family":"Bello","sequence":"additional","affiliation":[{"name":"CSIC , , Juan de la Cierva 3 , ,","place":["Madrid, Spain, 28006"]},{"name":"Universidade Federal do Rio de Janeiro , , ,","place":["Rio de Janeiro, Brazil, 21949-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepcio\u0301n","family":"Perez","sequence":"additional","affiliation":[{"name":"CSIC , , Juan de la Cierva 3 , ,","place":["Madrid, Spain, 28006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole F.","family":"Liachko","sequence":"additional","affiliation":[{"name":"Veterans Affairs Puget Sound Health Care System , , , ,","place":["Seattle, Washington, United States, 98108"]},{"name":"University of Washington , , , ,","place":["Seattle, Washington, United States, 98104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Kraemer","sequence":"additional","affiliation":[{"name":"Veterans Affairs Puget Sound Health Care System , , , ,","place":["Seattle, Washington, United States, 98108"]},{"name":"University of Washington , , , ,","place":["Seattle, Washington, United States, 98104"]},{"name":"University of Washington , , , ,","place":["Seattle, Washington, United States, 98195"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Miguel","sequence":"additional","affiliation":[{"name":"Inserm, U1079 , ,","place":["Rouen, France, 76183"]},{"name":"Normandie Univ (University of Rouen) , , ,","place":["Rouen, France, 76183"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magalie","family":"Lecourtois","sequence":"additional","affiliation":[{"name":"Inserm, U1079 , ,","place":["Rouen, France, 76183"]},{"name":"Normandie Univ (University of Rouen) , , ,","place":["Rouen, France, 76183"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Gil","sequence":"additional","affiliation":[{"name":"CSIC , , Juan de la Cierva 3 , ,","place":["Madrid, Spain, 28006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Martinez","sequence":"additional","affiliation":[{"name":"CSIC , , Juan de la Cierva 3 , ,","place":["Madrid, Spain, 28006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel I.","family":"Perez","sequence":"additional","affiliation":[{"name":"CSIC , , Juan de la Cierva 3 , ,","place":["Madrid, Spain, 28006"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,3,4]]},"reference":[{"key":"2026090204240993300_cit1","first-page":"CD001447","article-title":"Riluzole for amyotrophic\nlateral sclerosis (ALS)\/motor neuron disease (MND)","author":"Miller","year":"2007","journal-title":"Cochrane Database Syst. Rev."},{"key":"2026090204240993300_cit2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nrn3430","article-title":"The changing scene\nof amyotrophic lateral sclerosis","volume":"14","author":"Robberecht","year":"2013","journal-title":"Nature Rev.\nNeurosci."},{"key":"2026090204240993300_cit3","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1001\/archneur.63.2.262","article-title":"The G93C mutation\nin superoxide dismutase 1: clinicopathologic phenotype and prognosis","volume":"63","author":"Regal","year":"2006","journal-title":"Arch. Neurol."},{"key":"2026090204240993300_cit4","first-page":"Article ID 187234","article-title":"Progress\nin therapy development for amyotrophic lateral sclerosis","volume":"2012","author":"Venkova-Hristova","year":"2012","journal-title":"Neurol. Res. Int."},{"key":"2026090204240993300_cit5","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/362059a0","article-title":"Mutations in Cu\/Zn superoxide dismutase\ngene are associated with familial amyotrophic lateral sclerosis","volume":"362","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"2026090204240993300_cit6","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/ng.132","article-title":"TARDBP mutations\nin individuals with sporadic and familial amyotrophic lateral sclerosis","volume":"40","author":"Kabashi","year":"2008","journal-title":"Nature Genet."},{"key":"2026090204240993300_cit7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC\nhexanucleotide repeat in noncoding region of C9ORF72 causes chromosome\n9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"key":"2026090204240993300_cit8","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide\nrepeat expansion in C9ORF72 is the cause of chromosome 9p21-linked\nALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"2026090204240993300_cit9","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal\nlobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"2026090204240993300_cit10","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1126\/science.1154584","article-title":"TDP-43 mutations\nin familial and sporadic amyotrophic lateral sclerosis","volume":"319","author":"Sreedharan","year":"2008","journal-title":"Science"},{"key":"2026090204240993300_cit11","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1093\/hmg\/ddq230","article-title":"Neurotoxic effects\nof TDP-43 overexpression in C. elegans","volume":"19","author":"Ash","year":"2010","journal-title":"Hum. 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Neurochem."},{"key":"2026090204240993300_cit26","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/43830","article-title":"Casein\nkinase I\ntransduces Wnt signals","volume":"401","author":"Peters","year":"1999","journal-title":"Nature"},{"key":"2026090204240993300_cit27","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.cellsig.2004.12.011","article-title":"The casein kinase 1\nfamily: participation in multiple\ncellular processes in eukaryotes","volume":"17","author":"Knippschild","year":"2005","journal-title":"Cell. Signalling"},{"key":"2026090204240993300_cit28","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1002\/med.20207","article-title":"Protein kinases\nCK1 and CK2 as new targets for neurodegenerative\ndiseases","volume":"31","author":"Perez","year":"2011","journal-title":"Med. Res. 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