PF-3644022

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PF-3644022

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

1276121-88-0

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，K_i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。

生物活性

PF-3644022 is a potent, selective, orally active and ATP-competitiveMAPKAPK2 (MK2)inhibitor with anIC₅₀of 5.2 nM and aK_iof 3 nM. PF-3644022 also inhibits MK3 andp38 regulated/activated kinase (PRAK)withIC₅₀s of 53 nM and 5.0 nM, respectively. PF-3644022 potently inhibits TNFα production and has anti-inflammatory effect^[1].

IC₅₀& Target

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

体外研究
(In Vitro)

The inhibitory activity of PF-3644022 against other MAPKAP kinase family members is evaluated. Other than MNK2 with anIC₅₀of 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 (IC₅₀of 160 nM). PF-3644022 blocks TNFα and IL-6 production in LPS-stimulated human whole blood withIC₅₀values 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].

体内研究
(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 ED₅₀value of 20 mg/kg^[1].

Animal Model:	Female Lewis rats (125-140 g) injected with streptococcal cell wall^[1]
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.

分子量

374.46

性状

Solid

Formula

C₂₁H₁₈N₄OS

CAS 号

1276121-88-0

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

溶解性数据

In Vitro:

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

配制储备液

浓度溶剂体积质量

1 mg

5 mg

10 mg

1 mM	2.6705 mL	13.3526 mL	26.7051 mL
5 mM	0.5341 mL	2.6705 mL	5.3410 mL
10 mM	0.2671 mL	1.3353 mL	2.6705 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline)
Solubility: 2.08 mg/mL (5.55 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (5.55 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

*以上所有助溶剂都可在本网站选购。