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PD98059

PD98059 是一種非ATP競(jìng)爭(zhēng)性的MEK抑制劑，無(wú)細(xì)胞試驗(yàn)中IC50為2 μM，特異性抑制MEK-1介導(dǎo)的MAPK激活；不直接抑制ERK1或ERK2。PD98059 是一種aryl hydrocarbon receptor (AHR)的配體并起到拮抗劑的功能。

PD98059 Chemical Structure

PD98059 Chemical Structure

CAS: 167869-21-8

規(guī)格 價(jià)格 庫(kù)存 購(gòu)買數(shù)量
10mM (1mL in DMSO) 1570 現(xiàn)貨
10mg 1213.08 現(xiàn)貨
50mg 3845.73 現(xiàn)貨
200mg 5489.52 現(xiàn)貨
1g 10401.3 現(xiàn)貨
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PD98059相關(guān)產(chǎn)品

相關(guān)信號(hào)通路圖

MEK Signaling Pathways

MEK信號(hào)通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系 實(shí)驗(yàn)類型 給藥濃度 孵育時(shí)間 活性描述 文獻(xiàn)信息
NUGC2 Function Assay 50 μM 48 h increases expression of HLA-A02 or HLA-A24 molecules 24244023
SGC-7901? Apoptosis Assay 20 μM 24 h inhibits CP-mediated apoptosis 24241351
MG-63 Function Assay 20 μM 0.5 h blocks the CH-induced phosphorylated ELK1 protein expression 24239640
HCT-15 Apoptosis Assay 1 h abolishes the protective effects of PGE2?against curcumin-induced apoptosis 25431425
786-O Apoptosis Assay 50?μM 24 h potentiates?the pro-apoptotic effects of NC 24508476
HepG2? Growth Inhibition Assay 20 μM 24 h suppresses TGF-β1-induced cell proliferation and invasion 25560488
SW480 Function Assay 20?μM 1?h reduces the expression of ATF3 protein 25447816
MDA-MB-231 Function Assay 25 μM 2-3 h decreases p-ERK1/2 and S100A4 expression 25555875
HepG2? Function Assay 10 μM 5 h blocks phosphorylated MAPKs induced by exogenous TGF-β1 25560488
MCF-7? Function Assay 10 μM 1 h inhibits IL-18-enhanced cell migration 25727011
H1355 Function Assay 25 μM 1 h blunts the B[a]P-induced increase in phospho-Chk1 and phospho-ERK expression 25769181
PC12 Function assay Inhibition of nerve growth factor-mediated MAP kinase activity in human PC12 cells, IC50 = 2 μM. 18077363
HT-29 Antiproliferative assay 5 days Antiproliferative activity against human HT-29 cells after 5 days by WST1 assay, IC50 = 4 μM. 25078316
IEC6 Function assay 5 mins Inhibition of MEK1/2 in rat IEC6 cells assessed as reduction in ERK1/2 loop phosphorylation dosed 30 mins before to stimulation with 10% serum for 5 mins by immunoblotting method, IC50 = 4.2 μM. 25078316
NG 108-15 Function assay Concentration required to abolish MAPK activity in mouse neuroblastoma and rat glioma hybrid NG 108-15 cells, Activity = 10 μM. 15537354
PC12 Function assay 10 uM 5 hrs Activation of Nrf2/ARE in rat PC12 cells assessed as HO-1 protein induction at 10 uM after 5 hrs pretreated with JNK inhibitor SP600125 for 1 hr before compound addition by Western blot analysis 21345685
SW480 Function Assay 10 μM 20 h suppresses the CRT activity 24324366
HEK 293 Function Assay 10 μM 5 h inhibits Wnt-induced β-catenin/TCF4 activity and nuclear β-catenin accumulation 24324366
HEK 293 Function Assay 10 μM 5 h suppresses the CRT activity 24324366
HL-60? Function Assay 10/20 μM 1 h inhibits the?N. chinensisextract?induced differentiation into granulocytes 24357020
HL-60 Function Assay 2 μM 16 h inhibits the association of pS621 Raf-1 and NFATc3, and the RA-induced phosphorylation of nuclear NFATc3 24330068
HeLa Function Assay 50 μM 0.5 h blocks TRX-1 nuclear migration and TXNIP down-regulation 24376827
HUVECs Function Assay 10?μM 1 h inhibits the HDL reduced COX-2 expression and PGI-2 release 24385109
MCF-7 Function Assay 10?μM 10/30 min reduces the UTP-dependent ERK phosphorylation 24390819
HGC-27 Apoptosis Assay 1 μM 1 h suppresses RAD001 plus MK-2206-induced cell viability loss 24416349
PC3? Apoptosis Assay 50 μM 0.5 h inhibits MHY-449-induced apoptosis? 24424889
HPAEpiCs? Function Assay 30 μM 1 h inhibits TNF-α stimulated p42/p44 MAPK phosphorylation 24441870
BeWo Function Assay 10?μM 2 h inhibits ERK1/2 24433846
A498 Apoptosis Assay 50?μM 24 h potentiates?the pro-apoptotic effects of NC 24508476
NHBE Function Assay 2/20 μM 2 h attenuates IL-33 stimulated CXCL8/IL-8 secretion 24479526
A375 Cell Invasion Assay 10–20 μM 24 h reduces melanoma cell invasion 24466036
HBMEC Function Assay 10 μM 1 h blocks VEGF-induced EphA2 expression 24458982
A549 Function Assay 30 μM 0.5 h inhibits thrombin-induced C/EBPβ Thr235?phosphorylation 24277696
HCSMCs Growth Inhibition Assay 10 μM 24 h blocks FABP4-induced HCASMC proliferation 24312381
PANC-1 Function Assay 20 μM 48 h inhibits the expression of Δ6D in response to the PPARδ?agonist? 24294133
Raji? Function Assay 10 μM 1 h blocks hsBAFF induced Erk1/2 phosphorylation 24269630
Raji? Growth Inhibition Assay 10 μM 1 h inhibits the basal or hsBAFF-stimulated cell proliferation and viability 24269630
TE5 Function Assay 50 μM 48 h upregulates the expression of HLA class I 24244023
TE1 Function Assay 50 μM 48 h upregulates the expression of HLA class I 24244023
TE3 Function Assay 50 μM 48 h upregulates the expression of HLA class I 24244023
KYSE30 Function Assay 20/50/100 μM 48 h inhibits p-Erk and wortmannin downregulated p-Akt in a dose-dependent manner 24244023
TE1 Function Assay 20/50/100 μM 48 h inhibits p-Erk and wortmannin downregulated p-Akt in a dose-dependent manner 24244023
TE4 Function Assay 20/50/100 μM 48 h inhibits p-Erk and wortmannin downregulated p-Akt in a dose-dependent manner 24244023
HT29 Function Assay 10 μM 2 h inhibits of JAK2, ERK1/2 and STAT3 phosphorylation 24265293
HepG2 Apoptosis Assay 20 μM 24 h inhibits ERK1/2 phosphorylation and enhances VB1-induced apoptosis 24247909
HepG2 Function Assay 20 μM 2 h enhances VB1-induced FOXO3a transcriptional activity 24247909
MDA-MB-231 Function assay 50 uM Downregulation of MMP9 in human MDA-MB-231 cells at 50 uM by Western blot analysis 22926226
MKN45 Apoptosis Assay 10 μM? 24 h increases the DAPT-induced cell apoptosis 23792588
BxPC-3 cells Growth Inhibition Assay 20?μM 0.5 h inhibits VEGF-A-regulated HUVEC growth and tube formation induced by PAR-2 AP 23764046
NB4? Apoptosis Assay 10/20/60 μM 1.5 h decreases cell viability co-treated 23735541
HepG2? Function Assay 20?μM 24 h inhibits the HO-1 protein expression co-treated 23707609
HUVECs Apoptosis Assay 2/4 μM 24/48 h induces cell death 23707520
KG-1? Apoptosis Assay 20?μM 12 h enhances cell apoptosis induced by S1 23706691
AML 1# Apoptosis Assay 20?μM 12 h enhances cell apoptosis induced by S1 23706691
A2780? Function Assay 20?μM 1 h blocks DTCD-induced DR5 expression 23696862
KYSE30 Function Assay 50 μM 48 h upregulates the expression of HLA class I 24244023
MKN45 Growth Inhibition Assay 10 μM? 24/48/72 h inhibits cell growth co-treated with DAPT 23792588
SGC7901 Growth Inhibition Assay 10 μM? 24/48/72 h inhibits cell growth co-treated with DAPT 23792588
MKN45 Function Assay 10 μM? 24 h inhibits the expression of phosphorylated ERK1/2 23792588
SGC7901 Apoptosis Assay 10 μM? 24 h increases the DAPT-induced cell apoptosis 23792588
HUASMCs Function Assay 10 μM? 24 h diminishes Ang II-caused SOCS3 mRNA and protein expression? 23816468
SGC7901 Function Assay 10 μM? 24 h inhibits the expression of phosphorylated ERK1/2 23792588
HUASMCs Function Assay 10 μM? 24 h inhibits Ang II-induced ERK1/2 phosphorylation level 23816468
LNCaP? Function Assay 10 μM? 1 h decreases the EGF upregulated p-YB-1 23838318
HUVECs Function Assay 25 μM 1 h increase NF-κB p65 nuclear translocation 23901008
HL60? Function Assay 20?μM 72 h inhibits -induced CD11b expression 23825585
NB4? Function Assay 10 μM? 72 h inhibits -induced CD11b expression 23825585
EPOR/CR3 Function Assay 50?μM 3 h reduces EPO and/or IL-3-induced the tyrosine phosphorylation? 23820731
COLO205 Apoptosis Assay 10/20/40 μM 24 h induces DNA ladder formation 24019108
BxPC-3 Function Assay 10 μM? 6 h increase miR-143 expression 23973710
HPAF-II Function Assay 10 μM? 6 h increase miR-143 expression 23973710
HepG2 Function Assay 40 μM 6/12 h inhibits the increase of p-ERK1 and p-c-Jun protein expression by PL 23942851
HL-60 Apoptosis Assay 50?μM 1 h rescues BA145 mediated apoptosis 23948751
SGC7901 Apoptosis Assay 20?μM 1 h inhibits apoptosis induced by IFN-α?and 5′-DFUR 24027750
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
MDA-MB-231 Function assay 50 uM Downregulation of MMP2 in human MDA-MB-231 cells at 50 uM by Western blot analysis 22926226
PC12 Function assay 10 uM 5 hrs Activation of Nrf2/ARE in rat PC12 cells assessed as HO-1 protein induction at 10 uM after 5 hrs pretreated with MEK1 inhibitor PD98059 for 1 hr before compound addition by Western blot analysis 21345685
HeLa Function assay 20 uM 3 hrs Inhibition of ERK1/2 phosphorylation in human HeLa cells at 20 uM after 3 hrs by Western blotting analysis 23570615
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
PC12 Function assay 10 uM 5 hrs Activation of Nrf2/ARE in rat PC12 cells assessed as HO-1 protein induction at 10 uM after 5 hrs pretreated with MEK2 inhibitor U0126 for 1 hr before compound addition by Western blot analysis 21345685
MCF-7 Function Assay 20 μM 1 h abolishes expression of phosphorylated ERK co-treatment with conjugate 24216289
7402 Apoptosis Assay 30 μM 5 d decreases cell proliferation 24211253
HT-29 Function Assay 20?μM 48 h reduces the BNIP3 expression pre-treated with 5-aza-dC 24211581
DLD-1? Function Assay 20?μM 48 h reduces the BNIP3 expression pre-treated with 5-aza-dC 24211581
7721 Apoptosis Assay 30 μM 5 d decreases cell proliferation 24211253
SGC7901? Apoptosis Assay 50?μM 24/48/72 h induces apoptosis combined with JAK2 shRNA 24178240
SMMC7721 Function Assay 25/50 μM 24 h suppresses the expression of p-Akt or p-ERK1/2? 24168056
MCF-7 Growth Inhibition Assay 10 μM 48h reverses BNF-induced cell cycle arrest 24163404
Caco-2 Function Assay 50?μM 48h enhances the mRNA levels of?SCNN1A,FXYD3,?LCT,?LOX,?HIF3A,?ZG16,?PDE6A?and?LGALS16?genes?co-treated with Dex 24161695
HAECs Function Assay 10 μM 1 h ?attenuates TNF-α-stimulated ICAM-1 and VCAM-1 expression 24134657
Ca9-22 Function Assay 3 μM 1 h abolishes the ability of HbR to induce IL-8 production 24126532
Ca9-22 Function Assay 3 μM 1/2 h reduces HbR-induced ATF-2 phosphorylation 24126532
AGS Function Assay 10 μM? 0.5 h inhibits the upregulation of the IL-8 gene 24106166
Caco-2? Apoptosis Assay 10?μM 24?h decreases cell apoptosis induced by 5-FU 24095863
A549 Function Assay 50?μM 2 h blocks ERK phosphorylation mediated by 1,2-NQ 24067727
HPMC Function Assay 10?μM 48 h reverses the changes in cell morphology induced by HGPDS 24042838
HCT-8 Apoptosis Assay 10?μM 24?h decreases cell apoptosis induced by 5-FU 24095863
HPMC Apoptosis Assay 10?μM 24?h reverses decrease in cell viability induced by HGPDS 24042838
CRL-2302 Function Assay 20 μM 0.5 h inhibits Apelin-induced phosphorylation of Erk and Akt 24227918
MCF-7 Apoptosis Assay 20 μM 1 h increases caspase-9 enzyme activity 24216289
HCT-15 Function Assay 1 h attenuates PGE2-induced phosphorylation of Erk? 25431425
A549 Function Assay 30 μM 0.5 h inhibits the thrombin-induced IL-8/CXCL8-Luc activity 24277696
MC-3 Apoptosis Assay 10 μM 24 h potentiated MESC-induced apoptosis in cells 24270523
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
G292? Apoptosis Assay 30?μM 2 h restores capsaicin-induced cell death 24012930
MGC803? Apoptosis Assay 20?μM 1 h inhibits apoptosis induced by IFN-α?and 5′-DFUR 24027750
ARPE-19 Function Assay 20 μM 0.5 h inhibits Apelin-induced phosphorylation of Erk and Akt 24227918
NUGC3 Function Assay 50 μM 48 h increases expression of HLA-A02 or HLA-A24 molecules 24244023
OE19 Function Assay 50 μM 48 h increases expression of HLA-A02 or HLA-A24 molecules 24244023
NCI-N87? Function Assay 50 μM 48 h increases expression of HLA-A02 or HLA-A24 molecules 24244023
KATOIII? Function Assay 50 μM 48 h increases expression of HLA-A02 or HLA-A24 molecules 24244023
MKN7 Function Assay 50 μM 48 h increases expression of HLA-A02 or HLA-A24 molecules 24244023
TE4 Function Assay 50 μM 48 h upregulates the expression of HLA class I 24244023
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生物活性

產(chǎn)品描述 PD98059 是一種非ATP競(jìng)爭(zhēng)性的MEK抑制劑，無(wú)細(xì)胞試驗(yàn)中IC50為2 μM，特異性抑制MEK-1介導(dǎo)的MAPK激活；不直接抑制ERK1或ERK2。PD98059 是一種aryl hydrocarbon receptor (AHR)的配體并起到拮抗劑的功能。
特性 PD98059不會(huì)抑制已經(jīng)被c-Raf磷酸化的 MEK1
靶點(diǎn)
AhR [1]
(Cell-free assay)		 MEK1 [1]
(Cell-free assay)
1 μM 2 μM
體外研究(In Vitro)
體外研究活性

PD98059 要么抑制本底的MEK1，要么抑制一種被部分激活的MEK突變體，該突變體是 218 和 222號(hào)位上絲氨酸突變?yōu)楣劝彼岷笮纬傻?MEK-2E)， IC50 為2 μM. PD98059 不會(huì)抑制JNK和P38這兩個(gè) MAPK 的同系物. PD98059會(huì)高度選擇性的抑制MEK, 因?yàn)閷?duì)其它包括Raf 激酶, cAMP-依賴性激酶, 蛋白激酶C, v-Src, 表皮生長(zhǎng)因子 (EGF) 受體激酶, 胰島素受體激酶, PDGF 受體激酶, 和磷脂酰肌醇(-3)激酶等在內(nèi)的一系列激酶都沒有抑制性。 PD98059 會(huì)抑制經(jīng)過PDGF刺激而活化的MAPK 和胸苷 進(jìn)入 3T3 細(xì)胞， IC50分別為 ~10 μM 和 ~7 μM [1]。PD98059可以有效地阻止 MEK1 被Raf 或者M(jìn)EK 激酶活化， IC50為4 μM, 可以微弱地 抑制MEK2被 Raf 活化， IC50 為50 μM。 在KB 和 PC12 細(xì)胞中, PD98059 不會(huì)抑制MKK4 和RK激酶這兩個(gè)參與壓力和白細(xì)胞介素-1介導(dǎo)的激酶級(jí)聯(lián)反應(yīng)的MEK的同系物的活化，在Swiss 3T3 細(xì)胞中也不會(huì)通過胰島素或者表皮生長(zhǎng)因子抑制p70 S6 激酶的活化[2]。PD98059會(huì)在不改變細(xì)胞生存能力的情況下完全阻斷 神經(jīng)生長(zhǎng)因子(NGF)誘導(dǎo)的 PC12 細(xì)胞的分化[3] 。PD98059會(huì)以劑量依賴性的方式抑制培養(yǎng)在含有破骨細(xì)胞分化因子培養(yǎng)基中的 RAW264.7細(xì)胞的增值，進(jìn)而導(dǎo)致TRAP陽(yáng)性細(xì)胞數(shù)量明顯下降[6]。
激酶實(shí)驗(yàn) 體外MEK激酶活性測(cè)定
在含有44-kDa GST-MAPK 或者45-kDa GST-MEK1的體系中檢測(cè)32P被摻入蛋白 MBP中的情況。 反應(yīng)體系50 μL ，含有50 mM Tris, pH 7.4/10 mM MgCl2/2 mM EGTA/10 μM [γ-32P]ATP， 加入10 μg GST-MEK1, 0.5 μg GST-MAPK和 40 μg MBP。30°C 孵育15 分鐘, 加入Laemmli SDS 樣品緩沖液終止反應(yīng)。磷酸化的MBP 進(jìn)行10% SDS-PAGE分析
細(xì)胞實(shí)驗(yàn) 細(xì)胞系 K-Balb, KNRK, v-raf-3Y1, SRA/3Y1, EGFR/3T3, 和K562
濃度 溶于DMSO, 終濃度~100 μM
孵育時(shí)間 3 天, 或者7-10天
方法

細(xì)胞按10,000-20,000個(gè)/mL的密度接種在多孔平板中進(jìn)行單層生長(zhǎng)。48小時(shí)后把不同濃度的PD98059 加到細(xì)胞培養(yǎng)基孵育3天。 然后通過胰酶將細(xì)胞從平板中消化下來(lái)并用Coulter 計(jì)數(shù)器計(jì)數(shù)。 將細(xì)胞按5,000-10,000每皿的濃度接種在35 mm的培養(yǎng)皿中，培養(yǎng)基中含有0.3% 的瓊脂和期望濃度的PD98059，讓細(xì)胞在軟瓊脂上生長(zhǎng).經(jīng)過7-10天的生長(zhǎng), 可以借助解剖顯微鏡將可見的菌落數(shù)出來(lái)。
實(shí)驗(yàn)圖片 檢測(cè)方法 檢測(cè)指標(biāo) 實(shí)驗(yàn)圖片 PMID
Western blot c-Jun / α-tubulin / p-ERK / ERK / p-AKT / AKT p-JNK / JNK / Cyclin D1 p-HER2 / HER2 MMP9 / XIAP / VEGF 17482134
體內(nèi)研究(In Vivo)
體內(nèi)研究活性

在大腦缺血前30分鐘用PD98059處理小鼠可以明顯減輕傷害, 使腦梗塞的體積減小[4]?；谝认俚臐裰睾徒M織學(xué)研究發(fā)現(xiàn)，提前30分鐘用PD98059預(yù)處理 (10 mg/kg 靜脈注射) 然后每小時(shí)注射一次蛙皮素連續(xù)三次的小鼠可以明顯改善蛙皮素誘導(dǎo)的急性胰腺炎[7]?？ɡz損傷一小時(shí)后用PD98059 (10 mg/kg) 對(duì)小鼠進(jìn)行治療可以發(fā)現(xiàn)與炎癥相關(guān)的所有指標(biāo)均有所下降[11]。
動(dòng)物實(shí)驗(yàn) Animal Models 患有急性胰腺炎的雄性Sprague–Dawley 大鼠
Dosages 10 mg/kg
Administration 靜脈注射

化學(xué)信息&溶解度

分子量 267.28 分子式

C16H13NO3
CAS號(hào) 167869-21-8 SDF Download PD98059 SDF
Smiles COC1=CC=CC(=C1N)C2=CC(=O)C3=CC=CC=C3O2
儲(chǔ)存條件(自收到貨起)

體外溶解度
批次：

DMSO : 46 mg/mL ( (172.1 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

 動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量 濃度 體積 分子量

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過程中的損耗，建議多配一只動(dòng)物的藥量）

mg/kg g μL 只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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常見問題及建議解決方法

問題 1:
How to formulate this inhibitor for i.p. injection?

回答：
You can prepare the stock by the vehicle 30% PEG400/0.5% Tween80/5% Propylene glycol, 0.5% CMC.

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