BAY-826

Protein target name:

TIE1, TEK, DDR1, DDR2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

~~500 nM~~

Reviewer suggested Concentration for use in cells:

~13 nM

Probe Availability

TOCRIS

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

Tyrosine-protein Kinase

HUGO symbol:

HGNC:11809 HGNC:11724 HGNC:2730 HGNC:2731

Entrez gene ID:

7075 7010 780 4921

Target alias:

CD202B, GLC3E, TIE-2, TIE2, VMCM, VMCM1, JTK14, TIE, CAK, CD167, DDR, EDDR1, HGK2, MCK10, NEP, NTRK4, PTK3, PTK3A, RTK6, TRKE, MIG20a, NTRKR3, TKT, TYRO10, WRCN

Probe Details

Probe alias:

BAY826

PubChem CID:

71623052

SMILES string:

Cc1cc(C)c(cc1NC(c1cc(C#N)cc(c1)S(F)(F)(F)(F)F)=O)n1ccn2c1cc(c1cccnc1)n2

InChi Key:

MPASHPJAIUOWCK-UHFFFAOYSA-N

Control compound:

BAY-309

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

KD, IC50

1.6 nM KD, 0.45 nM IC50

Potency assay:

Affinity for TIE2 was achieved through KINOMEscan and in house kinase assay

Structure-activity relationship:

yes

Off target activity

Selectivity against non-family targets:

Selective within the kinome, closest off-targets in cells: STK10 (4.5 µM), EPHG6 (4.5 µM), LYN (10 µM)

In cell validation

On target activity in cells

Potency in cells:

IC50

2.7 nM TIE10.7 nM TEK3.0 nM DDR14.5 nM DDR2

Potency assay (cells):

Functional cellular assays: NanoBRET assay

Off target activity in cells

Selectivity against nonfamily targets (cells):

LeadProfilingScreen: no inhibition below 1 µM

In vivo validation

Organism:

Rat

Dose:

25, 50, 100 mg/Kg

Route of delivery:

Oral

Systemic clearance:

1.91 L/h/Kg

Fraction of probe bound to plasma protein:

54%

Primary Reference

Reference (doi):

10.1111/jnc.13877

Reference (PMID):

27787897

Part of the Donated Chemical Probes initiative from SGC.

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

SAB Rating

Rating for use in Cells

1 review(s)

Rating for use in Model Organisms

1 review(s)

SAB Members

SAB 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.

Jun 15 2020 - 12:21pm

BAY-826

Probe Availability

Probe Information

Target Details

CD202B, GLC3E, TIE-2, TIE2, VMCM, VMCM1, JTK14, TIE, CAK, CD167, DDR, EDDR1, HGK2, MCK10, NEP, NTRK4, PTK3, PTK3A, RTK6, TRKE, MIG20a, NTRKR3, TKT, TYRO10, WRCN

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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BAY-826

Probe Availability

Probe Information

Target Details

CD202B, GLC3E, TIE-2, TIE2, VMCM, VMCM1, JTK14, TIE, CAK, CD167, DDR, EDDR1, HGK2, MCK10, NEP, NTRK4, PTK3, PTK3A, RTK6, TRKE, MIG20a, NTRKR3, TKT, TYRO10, WRCN

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?