5FDP

Structure of DDR1 receptor tyrosine kinase in complex with D2099 inhibitor at 2.25 Angstroms resolution.

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.191 

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Ligand Structure Quality Assessment 


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


Literature

Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.

Wang, Z., Bian, H., Bartual, S.G., Du, W., Luo, J., Zhao, H., Zhang, S., Mo, C., Zhou, Y., Xu, Y., Tu, Z., Ren, X., Lu, X., Brekken, R.A., Yao, L., Bullock, A.N., Su, J., Ding, K.

(2016) J Med Chem 59: 5911-5916

  • DOI: https://doi.org/10.1021/acs.jmedchem.6b00140
  • Primary Citation of Related Structures:  
    5FDP

  • PubMed Abstract: 

    The structure-based design of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as selective DDR1 inhibitors is reported. One of the representative compounds, 6j, binds to DDR1 with a Kd value of 4.7 nM and suppresses its kinase activity with an IC50 value of 9.4 nM, but it is significantly less potent for a panel of 400 nonmutated kinases. 6j also demonstrated reasonable pharmacokinetic properties and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary fibrosis model.

    • Organizational Affiliation: 

    State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , 190 Kaiyuan Avenue, Guangzhou 510530, China.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Epithelial discoidin domain-containing receptor 1337Homo sapiensMutation(s): 0 
Gene Names: DDR1, CAK, EDDR1, NEP, NTRK4, PTK3A, RTK6, TRKE
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q08345 (Homo sapiens)
Explore Q08345 
Go to UniProtKB:  Q08345
PHAROS:  Q08345
GTEx:  ENSG00000204580 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ08345
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5WR
Query on 5WR
Download Ideal Coordinates CCD File 
B [auth A](4~{S})-4-methyl-~{N}-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]-2-pyrimidin-5-yl-3,4-dihydro-1~{H}-isoquinoline-7-carboxamide
C28 H31 F3 N6 O
YXESXLYKZKCWFJ-LJQANCHMSA-N
PEG
Query on PEG
Download Ideal Coordinates CCD File 
C [auth A]DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
EDO
Query on EDO
Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A]		1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
5WR BindingDB:  5FDP IC50: min: 21, max: 38 (nM) from 2 assay(s)
Binding MOAD:  5FDP IC50: 309 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.191 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 45.3α = 90
b = 63.15β = 90
c = 107.67γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

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: 2016-06-08
    Type: Initial release
  • Version 1.1: 2018-01-24
    Changes: Structure summary
  • Version 1.2: 2024-01-10
    Changes: Data collection, Database references, Refinement description