{"method": "X-RAY DIFFRACTION", "mutation_s_field": "No", "ec_number": "", "description": "Analogues of diflunisal, an FDA-approved nonsteroidal antiinflammatory drug (NSAID), were synthesized and evaluated as inhibitors of transthyretin (TTR) aggregation, including amyloid fibril formation. Biophysical studies reveal that inhibitors dramatically slow tetramer dissociation (the rate-determining step of amyloidogenesis) over a duration of 168 h. This appears to be achieved through ground-state stabilization, which raises the kinetic barrier for tetramer dissociation.", "ligstr": "1FL:A:C13 H8 F2 O3:250.2:5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID:c1cc(c(cc1c2ccc(cc2F)F)C(=O)O)O:InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18):HUPFGZXOMWLGNK-UHFFFAOYSA-N;1FL:B:C13 H8 F2 O3:250.2:5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID:c1cc(c(cc1c2ccc(cc2F)F)C(=O)O)O:InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18):HUPFGZXOMWLGNK-UHFFFAOYSA-N", "pmid": "14711308", "remarks": "Human transthyretin (ttr) complexed with diflunisal", "amyloid_non_amyloid": "Non-amyloid", "type": "Inhibitor complex", "inchi": "InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)%%InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)", "resolution": "1.85", "species": "Homo sapiens", "secondary_structure": "GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEESTTSCCEEEEEEEEETTEEEEEEEEECCCC&GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHTTTCCCSEEEEEEEEEECCCCCCCEEEEEEEETTEEEEEEEECCCCC", "chain_id": "A%%B", "gene_names": "TTR, PALB", "r_value_free": "0.235", "pdb_id": "3D2T", "reference": "J Med Chem. 2004 Jan 15;47(2):355-74", "keyword": "Transthyretin", "protein_name": "Transthyretin", "ligand_formula": "C13 H8 F2 O3%%C13 H8 F2 O3", "peptide_protein_sequence": "chain-ID A: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE; chain-ID B: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE", "entry": "S-0206", "length": "127", "uniprot_ac": "P02766", "author": "Adamski-Werner, S.L., Palaninathan, S.K., Sacchettini, J.C., Kelly, J.W.", "ligand_smiles": "c1cc(c(cc1c2ccc(cc2F)F)C(=O)O)O%%c1cc(c(cc1c2ccc(cc2F)F)C(=O)O)O", "ligand_mw": "250.2%%250.2", "alternative_name": "ATTR, Prealbumin, TBPA", "ligand_name": "5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID%%5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID", "pdb_classification": "HORMONE", "global_stoichiometry": "Homo 4-mer - A4 ", "inchi_key": "HUPFGZXOMWLGNK-UHFFFAOYSA-N%%HUPFGZXOMWLGNK-UHFFFAOYSA-N", "ligand_id": "1FL%%1FL"}