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115 a.a.
Key reference
DOI no: 10.1021/jm0708735 J Med Chem 51:260-270 (2008) PubMed id: 18095641
Biochemical and structural evaluation of highly selective 2-arylbenzoxazole-based transthyretin amyloidogenesis inhibitors. S.M.Johnson, S.Connelly, I.A.Wilson, J.W.Kelly. ABSTRACT
To develop potent transthyretin (TTR) amyloidogenesis inhibitors that also display high binding selectivity in blood, it proves useful to systematically optimize each of the three substructural elements that comprise a typical inhibitor: the two aryl rings and the linker joining them. In the first study, described herein, structural modifications to one aryl ring were evaluated by screening a library of 2-arylbenzoxazoles bearing thyroid hormone-like aryl substituents on the 2-aryl ring. Several potent and highly selective amyloidogenesis inhibitors were identified that exhibit minimal thyroid hormone nuclear receptor and COX-1 binding. High resolution crystal structures (1.3-1.5 A) of three inhibitors ( 2f, 4f, and 4d) in complex with TTR were obtained to characterize their binding orientation. Collectively, the results demonstrate that thyroid hormone-like substitution patterns on one aryl ring lead to potent and highly selective TTR amyloidogenesis inhibitors that lack undesirable thyroid hormone receptor or COX-1 binding.
Literature references that cite this PDB file's key reference
PubMed id Reference
19644733 J.N.Buxbaum, and N.Reixach (2009).
Transthyretin: the servant of many masters.Cell Mol Life Sci, 66, 3095-3101.
19125186 T.Mairal, J.Nieto, M.Pinto, M.R.Almeida, L.Gales, A.Ballesteros, J.Barluenga, J.J.Pérez, J.T.Vázquez, N.B.Centeno, M.J.Saraiva, A.M.Damas, A.Planas, G.Arsequell, and G.Valencia (2009).
Iodine atoms: a new molecular feature for the design of potent transthyretin fibrillogenesis inhibitors.PLoS ONE, 4, e4124.
PDB codes: 3fc8 3fcb The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.
