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Article: Discovery of inhibitors of the mitotic kinase TTK based on N-(3-(3-sulfamoylphenyl)-1H-indazol-5-yl)-acetamides and carboxamides

TitleDiscovery of inhibitors of the mitotic kinase TTK based on N-(3-(3-sulfamoylphenyl)-1H-indazol-5-yl)-acetamides and carboxamides
Authors
Laufer, RadoslawNg, GraceLiu, YongPatel, Narendra Kumar B.Edwards, Louise G.Lang, YunhuiLi, Sze WanFeher, MiklosAwrey, Don E.Leung, GenieBeletskaya, IrinaPlotnikova, OlgaMason, Jacqueline M.Hodgson, RichardWei, XinMao, GuodongLuo, XunyiHuang, PingGreen, ErinKiarash, RezaLin, Dan Chi ChiaHarris-Brandts, MareesBan, FuqiangNadeem, VincentMak, Tak W.Pan, Guohua J.Qiu, WeiChirgadze, Nickolay Y.Pauls, Henry W.
KeywordsIndazolyl benzenesulfonamide
antimitotic agents
Tyrosine Threonine Kinase (TTK)
Mitotic kinase
Anticancer
Monopolar Spindle 1 kinase (Mps1)
Issue Date2014
Citation
Bioorganic and Medicinal Chemistry, 2014, v. 22, n. 17, p. 4968-4997 How to Cite?
DOI: http://dx.doi.org/10.1016/j.bmc.2014.06.027
AbstractTTK kinase was identified by in-house siRNA screen and pursued as a tractable, novel target for cancer treatment. A screening campaign and systematic optimization, supported by computer modeling led to an indazole core with key sulfamoylphenyl and acetamido moieties at positions 3 and 5, respectively, establishing a novel chemical class culminating in identification of 72 (CFI-400936). This potent inhibitor of TTK (IC50 = 3.6 nM) demonstrated good activity in cell based assay and selectivity against a panel of human kinases. A co-complex TTK X-ray crystal structure and results of a xenograft study with TTK inhibitors from this class are described. © 2014 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/292843
ISSN
0968-0896
2021 Impact Factor: 3.461
2020 SCImago Journal Rankings: 0.721
ISI Accession Number ID
WOS:000341293300047

 

DC FieldValueLanguage
dc.contributor.authorLaufer, Radoslaw-
dc.contributor.authorNg, Grace-
dc.contributor.authorLiu, Yong-
dc.contributor.authorPatel, Narendra Kumar B.-
dc.contributor.authorEdwards, Louise G.-
dc.contributor.authorLang, Yunhui-
dc.contributor.authorLi, Sze Wan-
dc.contributor.authorFeher, Miklos-
dc.contributor.authorAwrey, Don E.-
dc.contributor.authorLeung, Genie-
dc.contributor.authorBeletskaya, Irina-
dc.contributor.authorPlotnikova, Olga-
dc.contributor.authorMason, Jacqueline M.-
dc.contributor.authorHodgson, Richard-
dc.contributor.authorWei, Xin-
dc.contributor.authorMao, Guodong-
dc.contributor.authorLuo, Xunyi-
dc.contributor.authorHuang, Ping-
dc.contributor.authorGreen, Erin-
dc.contributor.authorKiarash, Reza-
dc.contributor.authorLin, Dan Chi Chia-
dc.contributor.authorHarris-Brandts, Marees-
dc.contributor.authorBan, Fuqiang-
dc.contributor.authorNadeem, Vincent-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorPan, Guohua J.-
dc.contributor.authorQiu, Wei-
dc.contributor.authorChirgadze, Nickolay Y.-
dc.contributor.authorPauls, Henry W.-
dc.date.accessioned2020-11-17T14:57:20Z-
dc.date.available2020-11-17T14:57:20Z-
dc.date.issued2014-
dc.identifier.citationBioorganic and Medicinal Chemistry, 2014, v. 22, n. 17, p. 4968-4997-
dc.identifier.issn0968-0896-
dc.identifier.urihttp://hdl.handle.net/10722/292843-
dc.description.abstractTTK kinase was identified by in-house siRNA screen and pursued as a tractable, novel target for cancer treatment. A screening campaign and systematic optimization, supported by computer modeling led to an indazole core with key sulfamoylphenyl and acetamido moieties at positions 3 and 5, respectively, establishing a novel chemical class culminating in identification of 72 (CFI-400936). This potent inhibitor of TTK (IC50 = 3.6 nM) demonstrated good activity in cell based assay and selectivity against a panel of human kinases. A co-complex TTK X-ray crystal structure and results of a xenograft study with TTK inhibitors from this class are described. © 2014 Elsevier Ltd. All rights reserved.-
dc.languageeng-
dc.relation.ispartofBioorganic and Medicinal Chemistry-
dc.subjectIndazolyl benzenesulfonamide-
dc.subjectantimitotic agents-
dc.subjectTyrosine Threonine Kinase (TTK)-
dc.subjectMitotic kinase-
dc.subjectAnticancer-
dc.subjectMonopolar Spindle 1 kinase (Mps1)-
dc.titleDiscovery of inhibitors of the mitotic kinase TTK based on N-(3-(3-sulfamoylphenyl)-1H-indazol-5-yl)-acetamides and carboxamides-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bmc.2014.06.027-
dc.identifier.pmid25043312-
dc.identifier.scopuseid_2-s2.0-84906937206-
dc.identifier.volume22-
dc.identifier.issue17-
dc.identifier.spage4968-
dc.identifier.epage4997-
dc.identifier.eissn1464-3391-
dc.identifier.isiWOS:000341293300047-
dc.identifier.issnl0968-0896-

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