PF-3644022

生物活性靶点体外研究体内研究 PF-3644022 试剂级价格

PF-3644022

CAS号:1276121-88-0
英文名:PF 3644022
中文名:PF-3644022
CBNumber:CB52596685
分子式:C21H18N4OS
分子量:374.46
MOL File:1276121-88-0.mol

PF-3644022化学性质

熔点 :>180°C (dec.)
沸点 :703.3±60.0 °C(Predicted)
密度 :1.298±0.06 g/cm3(Predicted)
储存条件 :2-8°C(protect from light)
溶解度 :DMSO (Slightly), Methanol (Slightly)
形态 :Solid
酸度系数(pKa) :13.51±0.40(Predicted)
颜色 :Off-White to Yellow

安全信息

海关编码 :2934999090

PF-3644022性质、用途与生产工艺

生物活性 PF-3644022 是一种有效的，选择性的，口服活性的，具有 ATP 竞争性的 MAPKAPK2 (MK2) 抑制剂，IC50 为 5.2 nM，Ki 为 3 nM。PF-3644022 还抑制 MK3 和 p38 调节/激活激酶 (PRAK)，IC50 分别为 53 nM 和 5.0 nM。PF-3644022 有效抑制 TNFα 的产生并具有抗炎作用。
靶点

IC50: 5.2 nM (MK2), 5.0 nM (PRAK) and 53 nM (MK3).
Ki: 3 nM (MK2)
体外研究

The inhibitory activity of PF-3644022 against other MAPKAP kinase family members is evaluated. Other than MNK2 with an IC ₅₀ 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 ( IC ₅₀ of 160 nM). PF-3644022 blocks TNFα and IL-6 production in LPS-stimulated human whole blood with IC ₅₀ 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.

体内研究

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 ED ₅₀ 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.