PD98059

生物活性

PD98059是一种非ATP竞争性的MEK抑制剂，IC50为2 μM，特异性抑制MEK-1介导的MAPK激活；PD98059 是一种 ERK1/2 信号的抑制剂。PD98059 要么抑制本底的MEK1，要么抑制一种被部分激活的MEK突变体，该突变体是 218 和 222号位上丝氨酸突变为谷氨酸后形成的(MEK-2E)， IC50 为2 μM. PD98059 不会抑制JNK和P38这两个 MAPK 的同系物. PD98059会高度选择性的抑制MEK, 因为对其它包括Raf 激酶, cAMP-依赖性激酶, 蛋白激酶C, v-Src, 表皮生长因子 (EGF) 受体激酶, 胰岛素受体激酶, PDGF 受体激酶, 和磷脂酰肌醇(-3)激酶等在内的一系列激酶都没有抑制性。 PD98059 会抑制经过PDGF刺激而活化的MAPK 和胸苷 进入 3T3 细胞， IC50分别为 ~10 μM 和 ~7 μM 。PD98059可以有效地阻止 MEK1 被Raf 或者MEK 激酶活化， IC50为4 μM, 可以微弱地 抑制MEK2被 Raf 活化， IC50 为50 μM。

实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）

细胞实验
细胞系	C-33 and C-81 cells
方法	Treatment with chemotherapeutic agents. Cells were seeded in 6-well culture plates in regular culture medium at a density of 2.5*105 and 1*105 cells/well for C-33 and C-81 cells, respectively, for 2 days and then fed with SR medium, i.e., PR-free RPMI-1640 medium containing 5% heat-inactivated CS-FBS, 1% glutamine and 0.5% gentamicin. Two days after steroid starvation, one set of attached cells was harvested and counted as day 0. The remaining cells were fed with fresh SR medium and treated with PD98059, U0126, vinorelbine, docetaxel or various combinations in which the dosage of each reagent was specified. Control cells were maintained in SR medium and received solvent alone without chemotherapeutic agents. Fresh SR medium with or without chemotherapeutic agents was added every 3 days. Treatment was continued for 3 or 6 days, as described in each figure legend. To quantify the inhibition of cell growth, attached cells were trypsinized and the cells counted with a Coulter counter. The number of cells in control sets that received solvent alone was designated as 100% for comparison. All experiments were done in triplicate and repeated at least twice.
浓度	0~10 μM
处理时间	3 or 6 days

动物实验
动物模型	acute lung injury in mice
配制	DMSO, then diluted with saline
剂量	10mg/kg
给药处理	i. p.

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量，需要将22.4 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。

化学数据

储备液配制

以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	3.7414 mL	18.707 mL	37.4139 mL
5 mM	0.7483 mL	3.7414 mL	7.4828 mL
10 mM	0.3741 mL	1.8707 mL	3.7414 mL

使用AbMole产品发表的文献

• 

  World J Gastroenterol. 2020 Jun 7;26(21):2810-2820.

  Gan Shen Fu Fang ameliorates liver fibrosis in vitro and in vivo by inhibiting the inflammatory response and extracellular signal-regulated kinase phosphorylation
  PD98059购买自AbMole

• 

  Environ Toxicol. 2020 Jun;35(6):673-682.

  Pomegranate Extract Inhibits Migration and Invasion of Oral Cancer Cells by Downregulating Matrix metalloproteinase-2/9 and Epithelial-Mesenchymal Transition
  PD98059购买自AbMole

• 

  Exp Cell Res. 2020 Jan 1;386(1):111719.

  Tim-3 suppresses the killing effect of Vγ9Vδ2 T cells on colon cancer cells by reducing perforin and granzyme B expression.
  PD98059购买自AbMole

• 

  Exp Eye Res. 2018 Nov;176:10-19.

  Rapamycin mediates mTOR signaling in reactive astrocytes and reduces retinal ganglion cell loss.
  PD98059购买自AbMole

客户产品验证及相关生物数据

	数据来源	Experimental Eye Research (2018). Figure 3. PD98059 (Abmole Bioscience, Houston, TX, USA)
	方法	Western blot
	细胞系	ONH astrocytes
	浓度	25 μM
	处理时间	1 h
	实验结果	PD98059 did not significantly reduce the level of p-S6 kinase phosphorylation, but LY294002 showed a robust blockade of its phosphorylation.

	数据来源	PLoS One (2015). Figure 3. PD98059
	方法	Western blot
	细胞系	The rats
	浓度	2.5 mcg/5 mcl
	处理时间	16 h
	实验结果	The increased level of ERK1/2 (44/42kDa) in CCI-exposed rats was not observed in group which received repeated administration PD98059

参考文献

Effect of PD98059, a selective MAPK3/MAPK1 inhibitor, on acute lung injury in mice.
Di Paola R, et al. Int J Immunopathol Pharmacol. 2009 Oct-Dec;22(4):937-50. PMID: 20074457.

PD98059 and U0126 activate AMP-activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway.
Dokladda K, et al. FEBS Lett. 2005 Jan 3;579(1):236-40. PMID: 15620719.

ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells.
Zelivianski S, et al. Int J Cancer. 2003 Nov 10;107(3):478-85. PMID: 14506750.

Mitogen-activated protein kinase kinase inhibitor PD98059 blocks the trans-activation but not the stabilization or DNA binding ability of hypoxia-inducible factor-1alpha.
Hur E, et al. Mol Pharmacol. 2001 May;59(5):1216-24. PMID: 11306706.