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PDBsum entry 3sww
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Hydrolase/hydrolase inhibitor
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PDB id
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3sww
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PDB id:
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| Name: |
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Hydrolase/hydrolase inhibitor
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Title:
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Crystal structure of human dpp-iv in complex with sa-(+)-3- (aminomethyl)-4-(2,4-dichlorophenyl)-6-(2-methoxyphenyl)- 2-methyl- 5h-pyrrolo[3,4-b]pyridin-7(6h)-one
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Structure:
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Dipeptidyl peptidase 4. Chain: a, b. Fragment: unp residues 39-766. Synonym: adabp, adenosine deaminase complexing protein 2, adcp-2, dipeptidyl peptidase iv, dpp iv, t-cell activation antigen cd26, tp103, dipeptidyl peptidase 4 membrane form, dipeptidyl peptidase iv membrane form, dipeptidyl peptidase 4 soluble form, dipeptidyl peptidase iv soluble form. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: dpp4, adcp2, cd26. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
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Resolution:
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2.00Å
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R-factor:
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0.199
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R-free:
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0.234
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Authors:
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H.E.Klei
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Key ref:
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W.Wang
et al.
(2011).
7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site.
Bioorg Med Chem Lett,
21,
6646-6651.
PubMed id:
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Date:
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14-Jul-11
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Release date:
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26-Oct-11
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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.
727 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
21:6646-6651
(2011)
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PubMed id:
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7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site.
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W.Wang,
P.Devasthale,
A.Wang,
T.Harrity,
D.Egan,
N.Morgan,
M.Cap,
A.Fura,
H.E.Klei,
K.Kish,
C.Weigelt,
L.Sun,
P.Levesque,
Y.X.Li,
R.Zahler,
M.S.Kirby,
L.G.Hamann.
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ABSTRACT
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Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are
described. The preferred stereochemistry of these atropisomeric biaryl analogs
has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and
DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant
improvement in insulin response after single doses of 3 and 10 μmol/kg in ob/ob
mice.
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Links
