6G5J
Secreted phospholipase A2 type X in complex with ligand
Summary for 6G5J
| Entry DOI | 10.2210/pdb6g5j/pdb |
| Descriptor | Group 10 secretory phospholipase A2, CALCIUM ION, (3~{R})-3-[3-[2-aminocarbonyl-6-(trifluoromethyloxy)indol-1-yl]phenyl]butanoic acid, ... (6 entities in total) |
| Functional Keywords | secretory phospholipase a2 type x spla2x spla2-x phospholipase enzyme inhibitor complex, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 37826.02 |
| Authors | Sandmark, J.,Oster, L. (deposition date: 2018-03-29, release date: 2018-09-05, Last modification date: 2024-10-23) |
| Primary citation | Giordanetto, F.,Knerr, L.,Nordberg, P.,Pettersen, D.,Selmi, N.,Beisel, H.G.,de la Motte, H.,Mansson, A.,Dahlstrom, M.,Broddefalk, J.,Saarinen, G.,Klingegard, F.,Hurt-Camejo, E.,Rosengren, B.,Wikstrom, J.,Wagberg, M.,Brengdahl, J.,Rohman, M.,Sandmark, J.,Akerud, T.,Roth, R.G.,Jansen, F.,Ahlqvist, M. Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1H-indol-1-yl]pyridine-2-yl}propanoic Acid. ACS Med Chem Lett, 9:600-605, 2018 Cited by PubMed Abstract: A lead generation campaign identified indole-based sPLA-X inhibitors with a promising selectivity profile against other sPLA isoforms. Further optimization of sPLA selectivity and metabolic stability resulted in the design of (-)-, a novel, potent, and selective sPLA-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (-)- was tested in an ApoE murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (-)- did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis. PubMed: 30034586DOI: 10.1021/acsmedchemlett.7b00507 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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