PD98059   中文名称: 2-(2-氨基-3-甲氧苯基)-4H-1-苯并呋喃-4-酮

MEK1 (IC50 = 2-7 μM); MEK2 (IC50 = 50 μM); ERK1; ERK2; Autophagy

PD98059 抑制基础 MEK1 或通过将残基 218 和 222 处的丝氨酸更改为谷氨酸 (MEK-2E) 而产生的部分激活的 MEK，IC50 为 2 M。MAPK 同源物 JNK 和 P38 不会以任何方式被 PD98059 抑制。 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-激酶只是 PD98059 不具备的一些其他激酶抑制。 PD98059 的 IC50 分别为 ~10 μM 和 ~7 μM，可阻断 PDGF 刺激的 MAPK 激活和胸苷掺入 3T3 细胞。 [1] PD98059 的 IC50 为 4 μM，这使得它有效抑制 Raf 或 MEK 激酶激活 MEK1，IC50 为 50 μM，这使得它弱抑制 Raf 激活 MEK2。在 KB 和 PC12 细胞以及 Swiss 3T3 细胞中，PD98059 不会阻止 MEK 同源物 MKK4 和 RK 激酶的激活，这些激酶参与应激和白细胞介素 1 刺激的激酶级联反应。 [2] PD98059完全阻止神经生长因子（NGF）引起的PC12细胞的分化，而不影响细胞活力。 [3] PD98059 在 RANKL 存在的情况下对 RAW264.7 细胞增殖的剂量依赖性抑制导致培养物中 TRAP 阳性细胞的明显减少。 [4]

对小鼠进行治疗 在局灶性脑缺血前 30 分钟给予 PD98059 以防止损伤时，梗塞体积会减少。 [5]根据胰腺湿重和组织学，在每小时一次的雨蛙素注射前 30 分钟给予 PD98059 预处理（每次静脉注射 10 毫克/千克），持续三小时可显着降低雨蛙素诱发的急性胰腺炎的严重程度。 [6]在角叉菜胶后一小时给予小鼠 PD98059（10 毫克/千克），可减少所有测量到的炎症参数。 [7]

为了测量 32P 掺入髓磷脂碱性蛋白 (MBP) 中，使用含有 44-kDa MAPK (GST-MAPK) 或 45-kDa MEK (GST-MEK1) 的谷胱甘肽 S-转移酶 (GST) 融合蛋白。测定在 50 μL 溶液中进行，该溶液含有 10 μg GST-MEK1、0.5 μg GST-MAPK 和 40 μg MBP，以及 50 mM Tris，pH 7.4、10 mM MgCl2、2 mM EGTA 和 10 μM [γ-32P]ATP。 30°C 孵育 15 分钟后，添加 Laemmli SDS 样品缓冲液可终止反应。通过使用 SDS/10% PAGE，磷酸化的 MBP 得以分离。

将细胞以 10,000–20,000/mL 的密度接种到多孔板中进行单层生长。 48小时后，向细胞生长培养基中添加不同浓度的PD98059，然后再孵育3天。胰蛋白酶孵育后，从孔中提取细胞并使用库尔特计数器进行计数。将细胞以每皿 5,000-10,000 个细胞的密度接种到 35 毫米培养皿中，生长培养基中含有所需浓度的 PD98059 和 0.3% 琼脂，以便在软琼脂中生长。生长 7-10 天后，使用解剖显微镜对可见菌落进行手动计数。

Male Sprague–Dawley rats with acute pancreatitis
10 mg/kg
Injection i.v.

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PD98059 (MEK1 Inhibitor) has been shown to act in vivo as a highly selective inhibitor of MEK1 activation and the MAP kinase cascade. In the present study, we have investigated the effects of PD98059, on the development of non-septic shock caused by zymosan in mice. Mice received either intraperitoneally zymosan (500mg/kg, administered i.p. as a suspension in saline) or vehicle (0.25ml/mouse saline). PD98059 (10mg/kg) was administered 1 and 6h after zymosan administration i.p. Organ failure and systemic inflammation in mice was assessed 18h after administration of zymosan and/or PD98059. Treatment of mice with PD98059 attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan. PD98059 also attenuated the lung, liver and pancreatic injury and renal dysfunction caused by zymosan as well as the increase of TNF-alpha and IL-1beta plasma levels caused by zymosan. Immunohistochemical analysis for inducible nitric oxide synthase (iNOS), nitrotyrosine, poly(ADP-ribose) (PAR), ICAM-1, P-selectin, Bax, Bcl-2 and FAS-ligand revealed positive staining in pancreatic and intestinal tissue obtained from zymosan-injected mice. The degree of staining for nitrotyrosine, iNOS, PAR, ICAM-1, P-selectin, Bax, Bcl-2 and FAS-ligand were markedly reduced in tissue sections obtained from zymosan-injected mice, which had received PD98059. Moreover treatment of mice with PD98059 (10mg/kg) attenuated the NF-kappaB activation and mitogen-activated protein kinases (MAPK) expression induced by zymosan injection. In addition, administration of zymosan caused a severe illness in the mice characterized by a systemic toxicity, significant loss of body weight and a 60% of mortality at the end of observation period. Treatment with PD98059 significantly reduced the development of systemic toxicity, the loss in body weight and the mortality (20%) caused by zymosan. This study provides evidence that PD98059 attenuates the degree of zymosan-induced non-septic shock in mice. Pharmacol Res. 2010 Feb;61(2):175-87.

[1]. Proc Natl Acad Sci U S A . 1995 Aug 15;92(17):7686-9.

[2]. J Biol Chem . 1995 Nov 17;270(46):27489-94.

[3]. J Biol Chem . 1995 Jun 9;270(23):13585-8.

[4]. J Biol Chem . 2002 Dec 6;277(49):47366-72.

[5]. Proc Natl Acad Sci U S A . 1999 Oct 26;96(22):12866-9.

[6]. Pancreas . 2002 Oct;25(3):251-9.

[7]. Int J Immunopathol Pharmacol . 2009 Oct-Dec;22(4):937-50.

[8]. Melanoma Res . 2001 Feb;11(1):11-9.

[9]. Int Immunopharmacol . 2007 Jan;7(1):36-45.

[10]. Int J Cancer . 2003 Nov 10;107(3):478-85.

[11]. Cancer Res . 2007 Apr 1;67(7):3210-9.

[12]. Mol Pharmacol . 1998 Mar;53(3):438-45.

2-(2-amino-3-methoxyphenyl)chromen-4-one is a member of the class of monomethoxyflavones that is 3'-methoxyflavone bearing an additional amino substituent at position 2'. It has a role as an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor and a geroprotector. It is a monomethoxyflavone and an aromatic amine.
PD-98059 is an inhibitor of MAP-kinase kinase activation.
2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one is a natural product found in Pestalotiopsis neglecta with data available.
MEK Inhibitor PD-98059 is a cell-permeable, selective mitogen-activated protein (MAP) kinase inhibitor which exhibits activity through the inhibition of the phosphorylation and activation of MAP kinase.

C16H13NO3

267.2793

267.089

C, 71.90; H, 4.90; N, 5.24; O, 17.96

167869-21-8

167869-21-8

4713

Light yellow to yellow solid powder

1.3±0.1 g/cm3

453.1±45.0 °C at 760 mmHg

170 °C

221.9±25.0 °C

0.0±1.1 mmHg at 25°C

1.652

2.43

65.46

O1C2=C([H])C([H])=C([H])C([H])=C2C(C([H])=C1C1C([H])=C([H])C([H])=C(C=1N([H])[H])OC([H])([H])[H])=O

QFWCYNPOPKQOKV-UHFFFAOYSA-N

nChI=1S/C16H13NO3/c1-19-14-8-4-6-11(16(14)17)15-9-12(18)10-5-2-3-7-13(10)20-15/h2-9H,17H2,1H3

2-(2-amino-3-methoxyphenyl)chromen-4-one

PD98059; PD 98059; PD098059; 2-(2-amino-3-methoxyphenyl)-4H-chromen-4-one; PD-98059; 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; PD 98,059; 2-(2-amino-3-methoxyphenyl)chromen-4-one; PD-98059

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 33.3~46 mg/mL (124.7~172.1 mM)
Ethanol: Insoluble (<1 mg/mL)
Water: Insoluble (<1 mg/mL)

配方 1 中的溶解度: 2.08 mg/mL (7.78 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浮液；超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 2 中的溶解度: 4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 1mg/mL

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配方 3 中的溶解度: 10 mg/mL (37.41 mM) in 50% PEG300 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。