PF-3644022

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PF-3644022 是一种有效、选择性、自由可逆、ATP 竞争性的 MAPKAP2 (MK2) 抑制剂，Ki 为 3 nM。

PF-3644022 is a potent and selective, freely reversible, ATP-competitive inhibitor of MAPKAP2 (MK2) with Ki of 3 nM; shows good selectivity against a panel of 200 human kinases; potently inhibits TNFα production with similar activity (IC50=160 nM) in U937 cells and hPBMCs, blocks TNFα and IL-6 production in LPS-stimulated human whole blood with IC50 of 1.6 and 10.3 uM, respectively; activite in the rat LPS-induced TNFalpha model and orally efficacious.

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.

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. Animal Model:Female Lewis rats (125-140 g) injected with streptococcal cell wall Dosage:3 mg/kg, 10 mg/kg, 30 mg/kg, 50 mg/kg, 100 mg/kg Administration:Oral gavage; twice a day; for 12 days Result:Showed dose-dependent inhibition of chronic paw swelling measured on day 21 after 12 days of oral dosing.

PF 3644022 | PF3644022

MAPK/ERK Signaling

MAPKAPK2 (MK2)

MAPKAPK2 (MK2)

Cancer

——

1276121-88-0

374.46

C21H18N4OS

>98% (HPLC)

In Vitro:?DMSO : 41.67 mg/mL (111.28 mM)

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

(10R)-9,10,11,12-Tetrahydro-10-methyl-3-(6-methyl-3-pyridinyl)-8H-[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one

(-20℃)

With Ice Pack

≥ 2 years