MK-0893   Click here for help

GtoPdb Ligand ID: 9135

Synonyms: compound 9m [PMID: 22708876] | MK 0893 | MK-0893-005 | MK0893 | N-[(4-{(1S)-1-[3-(3,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine
PDB Ligand
Compound class: Synthetic organic
Comment: MK-0893 is reported as a potent, reversible and competitive antagonist of the glucagon receptor, with anti-type II diabetes potential [2]. X-ray crystallography shows that MK-0893 in fact binds to an allosteric site outside the seven transmembrane bundle [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 93.45
Molecular weight 587.14
XLogP 8.01
No. Lipinski's rules broken 1
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Canonical SMILES COc1ccc2c(c1)ccc(c2)c1cc(nn1C(c1ccc(cc1)C(=O)NCCC(=O)O)C)c1cc(Cl)cc(c1)Cl
Isomeric SMILES COc1ccc2c(c1)ccc(c2)c1cc(nn1[C@H](c1ccc(cc1)C(=O)NCCC(=O)O)C)c1cc(Cl)cc(c1)Cl
InChI InChI=1S/C32H27Cl2N3O4/c1-19(20-3-5-21(6-4-20)32(40)35-12-11-31(38)39)37-30(18-29(36-37)25-14-26(33)17-27(34)15-25)24-8-7-23-16-28(41-2)10-9-22(23)13-24/h3-10,13-19H,11-12H2,1-2H3,(H,35,40)(H,38,39)/t19-/m0/s1
1. Jazayeri A, Doré AS, Lamb D, Krishnamurthy H, Southall SM, Baig AH, Bortolato A, Koglin M, Robertson NJ, Errey JC et al.. (2016)
Extra-helical binding site of a glucagon receptor antagonist.
Nature, 533 (7602): 274-7. [PMID:27111510]
2. Xiong Y, Guo J, Candelore MR, Liang R, Miller C, Dallas-Yang Q, Jiang G, McCann PE, Qureshi SA, Tong X et al.. (2012)
Discovery of a novel glucagon receptor antagonist N-[(4-{(1S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the treatment of type II diabetes.
J Med Chem, 55 (13): 6137-48. [PMID:22708876]