3KWF

human DPP-IV with carmegliptin (S)-1-((2S,3S,11bS)-2-Amino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-3-yl)-4-fluoromethyl-pyrrolidin-2-one

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Discovery of carmegliptin: A potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

Mattei, P., Boehringer, M., Di Giorgio, P., Fischer, H., Hennig, M., Huwyler, J., Kocer, B., Kuhn, B., Loeffler, B.M., Macdonald, A., Narquizian, R., Rauber, E., Sebokova, E., Sprecher, U.

(2010) Bioorg Med Chem Lett 20: 1109-1113

  • DOI: https://doi.org/10.1016/j.bmcl.2009.12.024
  • Primary Citation of Related Structures:  
    3KWF, 3OC0

  • PubMed Abstract: 

    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.

    • Organizational Affiliation: 

    F Hoffmann-La Roche Ltd, Pharma Research, CH-4070 Basel, Switzerland. [email protected]


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl peptidase 4
A, B
728Homo sapiensMutation(s): 0 
EC: 3.4.14.5
UniProt & NIH Common Fund Data Resources
Find proteins for P27487 (Homo sapiens)
Explore P27487 
Go to UniProtKB:  P27487
PHAROS:  P27487
GTEx:  ENSG00000197635 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27487
Glycosylation
Glycosylation Sites: 1
Go to GlyGen: P27487-1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
B1Q PDBBind:  3KWF IC50: 6.8 (nM) from 1 assay(s)
BindingDB:  3KWF IC50: 6.8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.626α = 90
b = 69.541β = 90
c = 423.039γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
REFMACrefinement
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-01-12
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary