PF-3644022

PF-3644022 is a potent, selective, orally active and ATP-competitive MAPKAPK2 (MK2) inhibitor with an IC50 of 5.2 nM and a Ki of 3 nM. PF-3644022 also inhibits MK3 and p38 regulated/activated kinase (PRAK) with IC50s of 53 nM and 5.0 nM, respectively. PF-3644022 potently inhibits TNFα production and has anti-inflammatory effect.

Product information

CAS Number: 1276121-88-0

Molecular Weight: 374.46

Formula: C21H18N4OS

Chemical Name: (15R)-15-methyl-5-(6-methylpyridin-3-yl)-11-thia-6, 14, 17-triazatetracyclo[8.8.0.0, .0, ]octadeca-1(10), 2, 4, 6, 8, 12(18)-hexaen-13-one

Smiles: CC1=CC=C(C=N1)C1C=CC2C(=CC=C3SC4C(=O)N[C@H](C)CNC=4C=23)N=1

InChiKey: CMWRPDHVGMHLSZ-GFCCVEGCSA-N

InChi: InChI=1S/C21H18N4OS/c1-11-3-4-13(10-22-11)15-6-5-14-16(25-15)7-8-17-18(14)19-20(27-17)21(26)24-12(2)9-23-19/h3-8,10,12,23H,9H2,1-2H3,(H,24,26)/t12-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 41.67 mg/mL (111.28 mM; ultrasonic and warming and heat to 80°C)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

The inhibitory activity of PF-3644022 against other MAPKAP kinase family members is evaluated. Other than MNK2 with an IC50 of 148 nM, other family members are largely not inhibited, showing at least several hundred-fold selectivity versus MK2. In the human U937 monocytic cell line or peripheral blood mononuclear cells, PF-3644022 potently inhibits TNFα production with similar activity (IC50 of 160 nM). PF-3644022 blocks TNFα and IL-6 production in LPS-stimulated human whole blood with IC50 values of 1.6 and 10.3 μM, respectively. Inhibition of TNFα in U937 cells and blood correlates closely with inhibition of phospho-heat shock protein 27, a target biomarker of MK2 activity.

In Vivo:

PF-3644022 (3-100 mg/kg; oral gavage; twice a day; for 12 days; Lewis rats) treatment shows dose-dependent inhibition of chronic paw swelling measured on day 21 after 12 days of oral dosing, with ED50 value of 20 mg/kg.

References:

1. Mourey RJ, et al. A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. J Pharmacol Exp Ther. 2010 Jun;333(3):797-807

Products are for research use only. Not for human use.