DDR-IN-1   Click here for help

GtoPdb Ligand ID: 9354

PDB Ligand
Compound class: Synthetic organic
Comment: DDR-IN-1 is a potent and selective discoidin domain receptor tyrosine kinase 1 (DDR1) inhibitor [1]. DDR1-IN-1 binds to DDR1 in the 'DFG-out' conformation and inhibits DDR1 autophosphorylation. It was a preclinical lead compound.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 73.91
Molecular weight 552.23
XLogP 4.2
No. Lipinski's rules broken 0
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Canonical SMILES CCN1CCN(CC1)Cc1ccc(cc1C(F)(F)F)C(=O)Nc1ccc(c(c1)Oc1ccc2c(c1)CC(=O)N2)C
Isomeric SMILES CCN1CCN(CC1)Cc1ccc(cc1C(F)(F)F)C(=O)Nc1ccc(c(c1)Oc1ccc2c(c1)CC(=O)N2)C
InChI InChI=1S/C30H31F3N4O3/c1-3-36-10-12-37(13-11-36)18-21-6-5-20(15-25(21)30(31,32)33)29(39)34-23-7-4-19(2)27(17-23)40-24-8-9-26-22(14-24)16-28(38)35-26/h4-9,14-15,17H,3,10-13,16,18H2,1-2H3,(H,34,39)(H,35,38)
Bioactivity Comments
In cells, DDR1-IN-1 inhibits basal DDR1 autophosphorylation with an EC50 of 86nM, but does not have a significant antiproliferative effect on DDR1 deregulated cancer cell lines below 10μM [1].
KinomeScan assessment revealed DDR1-IN-1 binding to ABL, KIT, and PDGFRβ, but this did not translate to enzyme inhibition.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
discoidin domain receptor tyrosine kinase 1 Primary target of this compound Hs Inhibitor Inhibition 7.0 pIC50 - 1
pIC50 7.0 (IC50 1.05x10-7 M) [1]
Description: In a Lanthascreen enzyme assay
discoidin domain receptor tyrosine kinase 2 Hs Inhibitor Inhibition 6.4 pIC50 - 1
pIC50 6.4 (IC50 4.13x10-7 M) [1]
Description: In a Lanthascreen enzyme assay