Home MAPK inhibitor - MAPKAPK2 inhibitor - TNF-alpha inhibitor PF-3644022 For research use only.

PF-3644022

PF-3644022 is a potent freely reversible ATP-competitive inhibitor of MAPKAPK2 (MK2) with an Ki of 3 nM. PF-3644022 also potently inhibits TNFα production with an IC50 of 160 nM.

PF-3644022 Chemical Structure

PF-3644022 Chemical Structure

CAS No. 1276121-88-0

Purity & Quality Control

Batch: S822401 DMSO]75 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.95%
99.95

PF-3644022 Related Products

Biological Activity

Description

PF-3644022 is a potent freely reversible ATP-competitive inhibitor of MAPKAPK2 (MK2) with an Ki of 3 nM. PF-3644022 also potently inhibits TNFα production with an IC50 of 160 nM.
Targets
MK2 [1] TNFα [1]
3 nM(Ki) 160 nM
In vitro
In vitro

PF-3644022 is a potent freely reversible ATP-competitive compound that inhibits Mitogen-activated protein kinase-activated protein kinase 2(MK2) activity with good selectivity when profiled against 200 human kinases. In the human U937 monocytic cell line or peripheral blood mononuclear cells, PF-3644022 potently inhibits TNFα production with similar activity. PF-3644022 blocks TNFα and IL-6 production in LPS-stimulated human whole blood.<sup><a class="sref" href="#s_ref">[1]</a></sup>
Kinase Assay In Vitro Kinase Assays and Inhibition Kinetics.
The kinase activity of MK2 is assayed by using fluorescently labeled heat shock protein 27 (HSP27) peptide and a Caliper LabChip 3000. Phosphorylated peptide is separated from substrate peptide electrophoretically and quantified. All kinase reactions are performed at room temperature in 20 mM HEPES, containing 10 mM MgCl2, 1 mM dithiothreitol, 0.01% bovine serum albumin, and 0.0005% Tween 20, pH 7.5. For endpoint experiments, reactions are terminated during the linear phase by the addition of 30 mM EDTA. The kinase selectivity experiments are performed with the MgATP concentration fixed at the Km(app) determined for each enzyme. The initial velocitie is determined in the presence and absence of PF-3644022 with ATP as the varied substrate while the HSP27 peptide concentration is held constant.
Cell Research Cell lines Human U937 monocytic cell line, hPBMCs
Concentrations 0.1 nM-100μM
Incubation Time 1 h
Method

U937 cells and hPBMCs are pretreated with PF-3644022 at varying concentrations for 1 h before LPS stimulation at 100 ng/ml. TNFα levels in U937 cell are measured at 4 h after LPS stimulation by using an electrochemoluminescence MesoScale Discovery TNF kit. In hPBMCs, TNFα and IL-6, IL-8 are measured at 16 h after LPS stimulation by using a four-plex human cytokine MSD plate.
In Vivo
In vivo

PF-3644022 displays good pharmacokinetic parameters in rats and is orally efficacious in both the rat acute LPS-induced TNFα model and the chronic streptococcal cell wall-induced arthritis model,with ED50 values of 6.9 and 20 mg/kg, respectively.<sup><a class="sref" href="#s_ref">[1]</a></sup>
Animal Research Animal Models LPS-induced acute endotoxemia inflammation model (adult male Lewis rats), chronic streptococcal cell wall-induced arthritis model (female Lewis rats)
Dosages 1 mg/kg
Administration Oral gavage

Chemical Information & Solubility

Molecular Weight 374.46 Formula

C21H18N4OS
CAS No. 1276121-88-0 SDF --
Smiles CC1CNC2=C(SC3=C2C4=C(C=C3)N=C(C=C4)C5=CN=C(C)C=C5)C(=O)N1
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 75 mg/mL ( (200.28 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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