5qij: Difference between revisions
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==CRYSTAL STRUCTURE OF MURINE 11B- HYDROXYSTEROIDDEHYDROGENASE COMPLEXED WITH 2-(3-(1-(4- CHLOROPHENYL)CYCLOPROPYL)-[1,2,4]TRIAZOLO[4,3-A]PYRIDIN-8- YL)PROPAN-2-OL== | ==CRYSTAL STRUCTURE OF MURINE 11B- HYDROXYSTEROIDDEHYDROGENASE COMPLEXED WITH 2-(3-(1-(4- CHLOROPHENYL)CYCLOPROPYL)-[1,2,4]TRIAZOLO[4,3-A]PYRIDIN-8- YL)PROPAN-2-OL== | ||
<StructureSection load='5qij' size='340' side='right' caption='[[5qij]], [[Resolution|resolution]] 2.65Å' scene=''> | <StructureSection load='5qij' size='340' side='right'caption='[[5qij]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5qij]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QIJ OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5qij]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QIJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QIJ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HJG:2-{3-[1-(4-chlorophenyl)cyclopropyl][1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol'>HJG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HJG:2-{3-[1-(4-chlorophenyl)cyclopropyl][1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol'>HJG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5qij FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qij OCA], [https://pdbe.org/5qij PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qij RCSB], [https://www.ebi.ac.uk/pdbsum/5qij PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qij ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/DHI1_MOUSE DHI1_MOUSE] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BMS-823778 (2), a 1,2,4-triazolopyridinyl-methanol derived analog, was identified as a potent and selective inhibitor of human 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) enzyme (IC50 = 2.3 nM) with >10,000-fold selectivity over 11beta-HSD-2. Compound 2 exhibits robust acute pharmacodynamic effects in cynomolgus monkeys (ED50 = 0.6 mg/kg) and in diet-induced obese (DIO) mice (ED50 = 34 mg/kg). Compound 2 also showed excellent inhibition in an ex vivo adipose DIO mouse model (ED50 = 5.2 mg/kg). Oral bioavailability ranges from 44% to 100% in preclinical species. Its favorable development properties, pharmacokinetics, high adipose-to-plasma concentration ratio, and preclinical pharmacology profile have prompted the evaluation of 2 for the treatment of type 2 diabetes and metabolic syndrome in phase 2 clinical trials. | |||
Discovery of Clinical Candidate BMS-823778 as an Inhibitor of Human 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD-1).,Li J, Kennedy LJ, Walker SJ, Wang H, Li JJ, Hong Z, O'Connor SP, Ye XY, Chen S, Wu S, Yoon DS, Nayeem A, Camac DM, Ramamurthy V, Morin PE, Sheriff S, Wang M, Harper TW, Golla R, Seethala R, Harrity T, Ponticiello RP, Morgan NN, Taylor JR, Zebo R, Maxwell B, Moulin F, Gordon DA, Robl JA ACS Med Chem Lett. 2018 Nov 13;9(12):1170-1174. doi:, 10.1021/acsmedchemlett.8b00307. eCollection 2018 Dec 13. PMID:30613321<ref>PMID:30613321</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5qij" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: | [[Category: Sheriff S]] | ||
Latest revision as of 12:24, 18 February 2026
CRYSTAL STRUCTURE OF MURINE 11B- HYDROXYSTEROIDDEHYDROGENASE COMPLEXED WITH 2-(3-(1-(4- CHLOROPHENYL)CYCLOPROPYL)-[1,2,4]TRIAZOLO[4,3-A]PYRIDIN-8- YL)PROPAN-2-OL
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