XMD8-87

ATP competitive inhibitor of TNK2

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

TNK2

ATP competitive inhibitor

up to 500 nM

Probe Availability:

In Vitro Validations

Uniprot ID: Q07912

Target Class: Protein kinase

Target SubClass: TK

Potency: KD, IC50

Potency Value: 15, 35.4 nM

Potency Assay: Ambit binding assay (KD), Invitrogen Kinase assay

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

Target aliases:

Activated CDC42 kinase 1, ACK1, TNK2, ACK1_HUMAN, ...

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency end-point : KD, IC50 BRK 37 nM, 47 nM

Potency assay (off target): Ambit binding assay, Invitrogen kinase assay

Probe Selectivity in Vitro:

CSF1R (330 nM Kd in Ambit binding assay, 428 nM IC50 in Invitrogen kinase assay); DCAMKL1 (280 nM Kd in Ambit binding assay); DCAMKL2 (690 nM Kd in Ambit binding assay, 3200 nM IC50 in Invitrogen kinase assay); FRK (96 nM Kd in Ambit binding assay, 264 nM IC50 in Invitrogen kinase assay); GAK (270 nM Kd in Ambit binding assay); TNK1 (110 nM Kd in Ambit binding assay)

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Although direct live cell target engagement was not determined, the cell-free and phenotypic data support use of this probe as a selective tool in cellular studies at the concentrations proposed.

(last updated: 10 Nov 2020 )

SERP Ratings

In Cell Rating

SERP Comments:

This probe is based on a well-known scaffold that has yielded inhibitors of various kinases, including the ones listed in the specificity section, and ERK5. The scaffold also has a known bromodomain inhibition activity (DOI: 10.1126/scisignal.aal2473). Any use of this inhibitor should also have controls from different structural classes that inhibit ERK5 (eg BAY-885) and BRDs (eg JQ1)

(last updated: 18 Feb 2021 )

SERP Ratings

In Cell Rating

SERP Comments:

The selectivity of XMD-8-87 is concerning with respect to BRK and FRK. If XMD-8-87 is to be used as a probe for ACK1, care must be exercised to exclude off-targets BRK and FRK. There is no data on non kinase off-targets reported.

(last updated: 19 Apr 2021 )