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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. Among authors: beconi m. J Med Chem. 2015 Apr 9;58(7):2967-87. doi: 10.1021/jm5013598. Epub 2015 Mar 19. J Med Chem. 2015. PMID: 25760409
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. Among authors: beconi m. J Med Chem. 2012 Feb 9;55(3):1021-46. doi: 10.1021/jm201310y. Epub 2012 Jan 27. J Med Chem. 2012. PMID: 22224594
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. Among authors: beconi m. J Med Chem. 2013 Dec 27;56(24):9934-54. doi: 10.1021/jm4011884. Epub 2013 Dec 5. J Med Chem. 2013. PMID: 24261862
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. Among authors: beconi mg. J Med Chem. 2015 Feb 12;58(3):1159-83. doi: 10.1021/jm501350y. Epub 2015 Jan 23. J Med Chem. 2015. PMID: 25590515
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. Among authors: beconi m. 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.
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. Among authors: beconi m. 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.
Oral administration of the pimelic diphenylamide HDAC inhibitor HDACi 4b is unsuitable for chronic inhibition of HDAC activity in the CNS in vivo.
Beconi M, Aziz O, Matthews K, Moumné L, O'Connell C, Yates D, Clifton S, Pett H, Vann J, Crowley L, Haughan AF, Smith DL, Woodman B, Bates GP, Brookfield F, Bürli RW, McAllister G, Dominguez C, Munoz-Sanjuan I, Beaumont V. Beconi M, et al. PLoS One. 2012;7(9):e44498. doi: 10.1371/journal.pone.0044498. Epub 2012 Sep 4. PLoS One. 2012. PMID: 22973455 Free PMC article.
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