3OC0

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

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.286 
  • R-Value Work: 0.236 

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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. patrizio.mattei@roche.com


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
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
B2Q
Query on B2Q
Download Ideal Coordinates CCD File 
G [auth A],
L [auth B]		(2S,3R,11bR)-3-butyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-amine
C19 H30 N2 O2
IYTDSNSLAQHLJL-HYVNUMGLSA-N
NAG
Query on NAG
Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
H [auth B]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
H [auth B],
I [auth B],
J [auth B],
K [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
B2Q BindingDB:  3OC0 IC50: min: 520, max: 710 (nM) from 2 assay(s)
PDBBind:  3OC0 IC50: 520 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.286 
  • R-Value Work: 0.236 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.561α = 90
b = 68.487β = 90
c = 421.411γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
CCP4model building
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CCP4phasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-08-25
    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: Advisory, Data collection, Derived calculations, Structure summary