PF3644022

Reagent Authentication Certificate:

Chemical Probes Portal PF3644022.pdf

Protein target name:

MAPKAPK2

Mechanism of action:

ATP-competitive inhbitor

Recommended Concentration for use in cells:

200-900 nM

Probe Availability

MilliporeSigma (PF3644022)

Tocris (952021-60-2)

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

CAMK

HUGO ID:

HGNC:6887

Entrez gene ID:

9261

UNIPROT ID:

P49137

Target alias:

MAPKAP-K2, MK-2, MK2

Probe Details

Chemical Probes Portal ID:

CPP82

PubChem CID:

44631903

ChEMBL ID:

CHEMBL1231206

SMILES string:

C[C@@H]1CNC2=C(C(=O)N1)SC3=C2C4=C(C=C3)N=C(C=C4)C5=CN=C(C=C5)C

InChi Key:

CMWRPDHVGMHLSZ-GFCCVEGCSA-N

PAINs evaluation:

PAINs free

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

3 nM

Potency assay:

KD = 5.9 nM IC50 = 5.2 nM

Off target activity

Potency (off target):

IC50

Off target protein and potency:

MK3 53 nMPRAK 53 nMMNK2 148 nMAMPK 117 nMBrSK1 187 nMBrSK2 90 nMCAMK2 70 nMDRAK1 71 nMPIM1 88 nMASK1 60 nMMER 76 nM

Potency assay (off target):

At 1 uM, PF3644022 inhibited 16 kinases > 50% out of a panel of 200.

In cell validation

On target activity in cells

Potency in cells:

IC50

0.2 uM

Potency assay (cells):

Inhibition of protein substrate phosphorylation. PF3644022 also inhibited TNFalpha production in human U937 or PBMCs with an IC50 = 159 nM.

Target engagement assay (cells):

Indirect: inhibition of protein substrate phosphorylation

Off target activity in cells

Potency assay, off target (cells):

PF36644022 did not interfere with phosphorylation of substrates for p38alpha or JNK.

In vivo validation

Organism:

Sprague-Dawley rat

Dose:

3 mg/kg

Route of delivery:

Oral

Plasma half life:

9.1 hr

Systemic clearance:

0.62 L/h/kg

Fraction of probe bound to plasma protein:

0.91

Cmax:

0.66 uM

Tmax:

0.17 hr

Primary Reference

Reference (doi):

10.1124/jpet.110.166173

Reference (PMID):

20237073

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

This compound was originally described by Pfizer in a publication in 2010 (J Pharmacol Exp Ther. 2010 Jun; 333(3): 797-807). It has high potency towards MK2 (Ki = 3 nM) as well as PRAK (IC50 = 5 nM), MK2 (IC50 = 53 nM) and MNK2 (IC50 = 148 nM). It did not have significant activity against most of the ~200 other kinases against which it was profiled. It had significant activity (IC50 <100 nM) against the following kinases: BRSK2, CAMKII, DRAK1, PIM1, PRAK, ASK1, and MER. It is not known to what extent it has activity outside the kinome.

Jun 29 2016 - 7:44pm

PF3644022 is not a super selective chemical probe. It may, however, represent one of the better choices for studying MAPKAPK2, as a selective chemical probe is not currently available in the literature.

Sep 9 2016 - 8:39pm

PF3644022

Probe Availability

Probe Information

Target Details

MAPKAP-K2, MK-2, MK2

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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PF3644022

Probe Availability

Probe Information

Target Details

MAPKAP-K2, MK-2, MK2

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?