XMD8-87

Protein target name:

ACK1

Mechanism of action:

ATP competitive inhibitor

Recommended Concentration for use in cells:

~~up to 2 uM~~

Reviewer suggested Concentration for use in cells:

up to 500 nM

Probe Availability

MedChemExpress

TOCRIS

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

HUGO ID:

HGNC:19297

Entrez gene ID:

10188

UNIPROT ID:

Q07912

Target alias:

ACK, TNK2

Probe Details

Chemical Probes Portal ID:

CPP2046

Probe alias:

ACK1-B19, B19

PubChem CID:

53322923

ChEMBL ID:

CHEMBL1672987

SMILES string:

O=C1C2=CC=CC=C2N(C)C3=NC(NC4=CC=C(N5CCN(C)CC5)C=C4OC)=NC=C3N1

InChi Key:

LGLHCXISMKHLIK-UHFFFAOYSA-N

Physico-chemical properties

NMR:

1H NMR (600 MHz, CD3OD) δ 7.83 (dd, J = 1.2, 7.8 Hz, 1H), 7.71 (s, 1H), 7.62-7.59 (m, 2H), 7.30 (d, J = 8.4 Hz, 1H), 7.26 (t, J = 7.2 Hz, 1H), 6.75 (d, J = 1.8 Hz, 1H), 6.66 (d, J = 7.2 Hz, 1H), 3.92-3.87 (m, 5H), 3.66-3.60 (m, 2H), 3.49 (s, 3H), 3.30-3.24 (m, 2H), 3.14-3.08 (m, 2H), 2.97 (s, 3H).

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

KD, IC50

15, 35.4 nM

Potency assay:

Ambit binding assay (KD), Invitrogen Kinase assay

Off target activity

Potency (off target):

KD, IC50

Off target protein and potency:

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)

In cell validation

On target activity in cells

Potency in cells:

IC50

38 nM (D163E); 113 nM (R806Q)

Potency assay (cells):

Phosphorylation inhibition assay

Primary Reference

Reference (doi):

10.1016/j.chembiol.2011.05.010 10.1158/0008-5472.CAN-15-0817

Reference (PMID):

21802008 26677978

External Resources

Available data:

Nathanael Gray Lab - Cancer Chemical Biology

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

no rating

SAB Members

SAB 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.

Nov 10 2020 - 12:28pm

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)

Feb 18 2021 - 8:43pm

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.

Apr 19 2021 - 11:52am

XMD8-87

Probe Availability

Probe Information

Target Details

ACK, TNK2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

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XMD8-87

Probe Availability

Probe Information

Target Details

ACK, TNK2

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?