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 K_i 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^[1].

IC50: 5.2 nM (MK2), 5.0 nM (PRAK) and 53 nM (MK3)^[1].
Ki: 3 nM (MK2)^[1]

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^[1].
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^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

374.46

Solid

C₂₁H₁₈N₄OS

1276121-88-0

O=C1C2=C(NC[[email protected]@H](C)N1)C3=C(C=CC4=NC(C5=CN=C(C)C=C5)=CC=C34)S2

Room temperature in continental US; may vary elsewhere.

• [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 Ex  [Content Brief]