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PDBsum entry 3oc0
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Structure of human dpp-iv with hts hit (2s,3s,11bs)-3-butyl-9,10- dimethoxy-1,3,4,6,7,11b-hexahydro-2h-pyrido[2,1-a]isoquinolin-2- ylamine
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Structure:
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Dipeptidyl peptidase 4. Chain: a, b. Synonym: dipeptidyl peptidase iv, dpp iv, t-cell activation antigen cd26, tp103, adenosine deaminase complexing protein 2, adcp-2, adabp, dipeptidyl peptidase 4 membrane form, dipeptidyl peptidase iv membrane form, dipeptidyl peptidase 4 soluble form, dipeptidyl peptidase iv soluble form. Ec: 3.4.14.5
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Source:
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Homo sapiens. Human. Organism_taxid: 9606
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Resolution:
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2.70Å
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R-factor:
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0.236
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R-free:
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0.286
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Authors:
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M.Hennig,M.Stihle,R.Thoma
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Key ref:
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P.Mattei
et al.
(2010).
Discovery of carmegliptin: a potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.
Bioorg Med Chem Lett,
20,
1109-1113.
PubMed id:
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Date:
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09-Aug-10
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Release date:
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25-Aug-10
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Supersedes:
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PROCHECK
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Headers
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References
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P27487
(DPP4_HUMAN) -
Dipeptidyl peptidase 4 from Homo sapiens
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Seq:
Struc:
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766 a.a.
728 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.4.14.5
- dipeptidyl-peptidase Iv.
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Reaction:
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Release of an N-terminal dipeptide, Xaa-Xbb-|-Xcc, from a polypeptide, preferentially when Xbb is Pro, provided Xcc is neither Pro nor hydroxyproline.
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Bioorg Med Chem Lett
20:1109-1113
(2010)
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PubMed id:
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Discovery of carmegliptin: a potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.
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P.Mattei,
M.Boehringer,
P.Di Giorgio,
H.Fischer,
M.Hennig,
J.Huwyler,
B.Koçer,
B.Kuhn,
B.M.Loeffler,
A.Macdonald,
R.Narquizian,
E.Rauber,
E.Sebokova,
U.Sprecher.
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ABSTRACT
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Design, synthesis, and SAR are described for a class of DPP-IV inhibitors based
on aminobenzo[a]quinolizines with non-aromatic substituents in the S1
specificity pocket. One representative thereof, carmegliptin (8p), was chosen
for clinical development. Its X-ray structure in complex with the enzyme and
early efficacy data in animal models of type 2 diabetes are also presented.
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Links
