BAY-826

Inhibitor of TIE1, TEK, DDR1, DDR2

Structure

Information

Protein target names: TIE1, TEK, DDR1, DDR2

Mechanism of action: Inhibitor

Recommended in-cell concentration:
~13 nM

In Vitro Validations

Uniprot ID: P35590
Target Class: Kinase
Target SubClass: TK
Potency: Kd
Potency Value: 0.9 nM
Potency Assay: KINOMEscan
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: yes
Target aliases:
Tyrosine-protein kinase receptor Tie-1, TIE, TIE1, ...

DOI Reference: 10.1111/jnc.13877

In Cell Validations

In Vivo Data

I have extra information to add

SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

TIE-1, DDR1, DDR2 and STK10/LOK are reported as the only kinases of 456 tested within 4x of TIE-2 potency.  Percent inhibition at 100 nM for the entire panel of kinases appears to have been disclosed to the SGC, or generated by the SGC, here: https://www.sgc-ffm.uni-frankfurt.de/chemProbes#!kinomescandataview/BAY-826.  P38a and EPHB6 appear to be additional selectivity concerns.

It should also be noted that the PD effect claimed was not consistently observed across all model systems, in part due to low Tie-2 expression in the tissues of interest, though the authors suggest differential sensitivity to a Tie-2 mechanism among the models tested may also contribute.  Regardless, additional in vivo validation would be valuable.

Rebastinib is likely the current pharmacologic standard for Tie-2, with considerably more characterization in the literature, some disclosed selectivity information (see Chembl in addition to primary literature), greater potency, lower in vivo dose, etc.  By contrast, the DOI reported here appears to be the only peer-reviewed article characterizing BAY-826.

Having said that, BAY-826 likely represents a chemically orthogonal tool for Tie-2 inhibition that would complement experiments with Rebastinib.

(last updated: 15 Jun 2020 )