DDR1-IN-1

Protein target name:

DDR1

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

50 nM - 200 nM

Probe Availability

Tocris (1449685-96-4)

MedChem Express (1449685-96-4)

Cayman (DDR1-IN-1 hydrate)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

HUGO ID:

HGNC:2730

Entrez gene ID:

780

UNIPROT ID:

Q08345

Target alias:

CAK, CD167, DDR, EDDR1, HGK2, MCK10, NEP, NTRK4, PTK3, PTK3A, RTK6, TRKE

Probe Details

Chemical Probes Portal ID:

CPP113

Probe alias:

BDBM104009, ZINC96174842, CS-2808

PubChem CID:

72836888

ChEMBL ID:

CHEMBL3421914

SMILES string:

CCN1CCN(CC1)CC2=C(C=C(C=C2)C(=O)NC3=CC(=C(C=C3)C)OC4=CC5=C(C=C4)NC(=O)C5)C(F)(F)F

InChi Key:

AOZPVMOOEJAZGK-UHFFFAOYSA-N

Orthogonal probe:

BAY-826

PAINs evaluation:

PAINs free

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

105 nM

Potency assay:

Lanthascreen

PDB ID for probe-target interaction (3D structure):

4CKR

Off target activity

Potency (off target):

IC50

Off target protein and potency:

DDR2 413 nM

Potency assay (off target):

KinomeScan binding assay revealed off-target activity against ABL, KIT and PDGFRbeta

In cell validation

On target activity in cells

Potency in cells:

EC50

86 nM

Potency assay (cells):

Collagen-dependent autophosphorylation in U2OS cells

Target engagement assay (cells):

Indirect: inhibition of autophosphorylation, and expression of a DDR1-IN-1-insensitive mutant (G707A) raised the EC50 by 20-fold.

Primary Reference

Reference (doi):

10.1021/cb400430t

Reference (PMID):

23899692

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

DDR1-IN-1 is selective across 451 kinases with selectivity score (S(1) at 1 uM) of 0.01, as assessed with the KinomeScan approach. It is more effective in combination with inhibitors against EGFR, SRC, CDK1, mTOR and PI3K, for example with GSK212458. The PK profile is modest with t1/2 = 2.76 hrs; CL = 89.88 (mL/min/kg); Vss = 18.02; and F = 26%. The compound is commercially available and accessible synthetically through a four step synthesis. X-ray crystal structure shows DDR1-IN-1 bound to DDR1 in the hinge binding area.

Jun 29 2016 - 7:52pm

DDR1-IN-1 has modest biochemical selectivity (4X) for DDR1 over DDR2, but shows excellent broader selectivity across the KinomeScan panel when tested at 1 uM (S(1) at 1 uM of 0.01). DDR1-IN-1 demonstrates only weak cellular potency (no antiproliferative effects at concentrations of <10 uM), and it is not clear if this is a limitation of the compound or reflective of the target biology. Positive combination effects are seen with other kinase inhibitors, such as GSK2126458 (a PI3K/mTOR inhibitor), implying that the compound is capable of engaging its target in cells. For now, DDR1-IN-1 appears to be an acceptable probe for DDR1-dependent signal transduction.

Jun 30 2016 - 3:57am

DDR1-IN-1

Probe Availability

Probe Information

Target Details

CAK, CD167, DDR, EDDR1, HGK2, MCK10, NEP, NTRK4, PTK3, PTK3A, RTK6, TRKE

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

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DDR1-IN-1

Probe Availability

Probe Information

Target Details

CAK, CD167, DDR, EDDR1, HGK2, MCK10, NEP, NTRK4, PTK3, PTK3A, RTK6, TRKE

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?