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Foundation-directed therapeutic development in Huntington's disease.
Dominguez C, Munoz-Sanjuan I. Dominguez C, et al. J Med Chem. 2014 Jul 10;57(13):5479-88. doi: 10.1021/jm4009295. Epub 2014 Feb 4. J Med Chem. 2014. PMID: 24432836
Optimization of Potent and Selective Ataxia Telangiectasia-Mutated Inhibitors Suitable for a Proof-of-Concept Study in Huntington's Disease Models.
Toledo-Sherman L, Breccia P, Cachope R, Bate JR, Angulo-Herrera I, Wishart G, Matthews KL, Martin SL, Cox HC, McAllister G, Penrose SD, Vater H, Esmieu W, Van de Poël A, Van de Bospoort R, Strijbosch A, Lamers M, Leonard P, Jarvis RE, Blackaby W, Barnes K, Eznarriaga M, Dowler S, Smith GD, Fischer DF, Lazari O, Yates D, Rose M, Jang SW, Muñoz-Sanjuan I, Dominguez C. Toledo-Sherman L, et al. J Med Chem. 2019 Mar 28;62(6):2988-3008. doi: 10.1021/acs.jmedchem.8b01819. Epub 2019 Mar 19. J Med Chem. 2019. PMID: 30840447
Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor.
Luckhurst CA, Aziz O, Beaumont V, Bürli RW, Breccia P, Maillard MC, Haughan AF, Lamers M, Leonard P, Matthews KL, Raphy G, Stott AJ, Munoz-Sanjuan I, Thomas B, Wall M, Wishart G, Yates D, Dominguez C. Luckhurst CA, et al. Bioorg Med Chem Lett. 2019 Jan 1;29(1):83-88. doi: 10.1016/j.bmcl.2018.11.009. Epub 2018 Nov 13. Bioorg Med Chem Lett. 2019. PMID: 30463802
Lead optimization toward proof-of-concept tools for Huntington's disease within a 4-(1H-pyrazol-4-yl)pyrimidine class of pan-JNK inhibitors.
Wityak J, McGee KF, Conlon MP, Song RH, Duffy BC, Clayton B, Lynch M, Wang G, Freeman E, Haber J, Kitchen DB, Manning DD, Ismail J, Khmelnitsky Y, Michels P, Webster J, Irigoyen M, Luche M, Hultman M, Bai M, Kuok ID, Newell R, Lamers M, Leonard P, Yates D, Matthews K, Ongeri L, Clifton S, Mead T, Deupree S, Wheelan P, Lyons K, Wilson C, Kiselyov A, Toledo-Sherman L, Beconi M, Muñoz-Sanjuan I, Bard J, Dominguez C. Wityak J, et al. J Med Chem. 2015 Apr 9;58(7):2967-87. doi: 10.1021/jm5013598. Epub 2015 Mar 19. J Med Chem. 2015. PMID: 25760409
Design, synthesis, and biological evaluation of potent and selective class IIa histone deacetylase (HDAC) inhibitors as a potential therapy for Huntington's disease.
Bürli RW, Luckhurst CA, Aziz O, Matthews KL, Yates D, Lyons KA, Beconi M, McAllister G, Breccia P, Stott AJ, Penrose SD, Wall M, Lamers M, Leonard P, Müller I, Richardson CM, Jarvis R, Stones L, Hughes S, Wishart G, Haughan AF, O'Connell C, Mead T, McNeil H, Vann J, Mangette J, Maillard M, Beaumont V, Munoz-Sanjuan I, Dominguez C. Bürli RW, et al. J Med Chem. 2013 Dec 27;56(24):9934-54. doi: 10.1021/jm4011884. Epub 2013 Dec 5. J Med Chem. 2013. PMID: 24261862
Exploiting differences in caspase-2 and -3 S₂ subsites for selectivity: structure-based design, solid-phase synthesis and in vitro activity of novel substrate-based caspase-2 inhibitors.
Maillard MC, Brookfield FA, Courtney SM, Eustache FM, Gemkow MJ, Handel RK, Johnson LC, Johnson PD, Kerry MA, Krieger F, Meniconi M, Muñoz-Sanjuán I, Palfrey JJ, Park H, Schaertl S, Taylor MG, Weddell D, Dominguez C. Maillard MC, et al. Bioorg Med Chem. 2011 Oct 1;19(19):5833-51. doi: 10.1016/j.bmc.2011.08.020. Epub 2011 Aug 16. Bioorg Med Chem. 2011. PMID: 21903398
Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.
Toledo-Sherman LM, Prime ME, Mrzljak L, Beconi MG, Beresford A, Brookfield FA, Brown CJ, Cardaun I, Courtney SM, Dijkman U, Hamelin-Flegg E, Johnson PD, Kempf V, Lyons K, Matthews K, Mitchell WL, O'Connell C, Pena P, Powell K, Rassoulpour A, Reed L, Reindl W, Selvaratnam S, Friley WW, Weddell DA, Went NE, Wheelan P, Winkler C, Winkler D, Wityak J, Yarnold CJ, Yates D, Munoz-Sanjuan I, Dominguez C. Toledo-Sherman LM, et al. J Med Chem. 2015 Feb 12;58(3):1159-83. doi: 10.1021/jm501350y. Epub 2015 Jan 23. J Med Chem. 2015. PMID: 25590515
Irreversible 4-Aminopiperidine Transglutaminase 2 Inhibitors for Huntington's Disease.
Prime ME, Brookfield FA, Courtney SM, Gaines S, Marston RW, Ichihara O, Li M, Vaidya D, Williams H, Pedret-Dunn A, Reed L, Schaertl S, Toledo-Sherman L, Beconi M, Macdonald D, Muñoz-Sanjuan I, Dominguez C, Wityak J. Prime ME, et al. ACS Med Chem Lett. 2012 Aug 9;3(9):731-5. doi: 10.1021/ml3001352. eCollection 2012 Sep 13. ACS Med Chem Lett. 2012. PMID: 24900540 Free PMC article.
SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease.
Wityak J, Prime ME, Brookfield FA, Courtney SM, Erfan S, Johnsen S, Johnson PD, Li M, Marston RW, Reed L, Vaidya D, Schaertl S, Pedret-Dunn A, Beconi M, Macdonald D, Muñoz-Sanjuan I, Dominguez C. Wityak J, et al. ACS Med Chem Lett. 2012 Oct 4;3(12):1024-8. doi: 10.1021/ml300241m. eCollection 2012 Dec 13. ACS Med Chem Lett. 2012. PMID: 24900424 Free PMC article.
Discovery and structure-activity relationship of potent and selective covalent inhibitors of transglutaminase 2 for Huntington's disease.
Prime ME, Andersen OA, Barker JJ, Brooks MA, Cheng RK, Toogood-Johnson I, Courtney SM, Brookfield FA, Yarnold CJ, Marston RW, Johnson PD, Johnsen SF, Palfrey JJ, Vaidya D, Erfan S, Ichihara O, Felicetti B, Palan S, Pedret-Dunn A, Schaertl S, Sternberger I, Ebneth A, Scheel A, Winkler D, Toledo-Sherman L, Beconi M, Macdonald D, Muñoz-Sanjuan I, Dominguez C, Wityak J. Prime ME, et al. J Med Chem. 2012 Feb 9;55(3):1021-46. doi: 10.1021/jm201310y. Epub 2012 Jan 27. J Med Chem. 2012. PMID: 22224594
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