alleen voor onderzoeksdoeleinden
Cat.nr.S1177
| Gerelateerde doelwitten | ERK p38 MAPK Raf JNK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase |
|---|---|
| Overig MEK Inhibitoren | PD0325901 (Mirdametinib) U0126-EtOH PD184352 (CI-1040) BIX 02189 Pimasertib (AS-703026) Refametinib (RDEA119) TAK-733 AZD8330 SL-327 BIX 02188 |
| Cellijnen | Assaytype | Concentratie | Incubatietijd | Formulering | Activiteitsbeschrijving | PMID |
|---|---|---|---|---|---|---|
| TE4 | Function Assay | 50 μM | 48 h | DMSO | upregulates the expression of HLA class I | 24244023 |
| MKN7 | Function Assay | 50 μM | 48 h | DMSO | increases expression of HLA-A02 or HLA-A24 molecules | 24244023 |
| OE19 | Function Assay | 50 μM | 48 h | DMSO | increases expression of HLA-A02 or HLA-A24 molecules | 24244023 |
| NCI-N87 | Function Assay | 50 μM | 48 h | DMSO | increases expression of HLA-A02 or HLA-A24 molecules | 24244023 |
| KATOIII | Function Assay | 50 μM | 48 h | DMSO | increases expression of HLA-A02 or HLA-A24 molecules | 24244023 |
| NUGC3 | Function Assay | 50 μM | 48 h | DMSO | increases expression of HLA-A02 or HLA-A24 molecules | 24244023 |
| NUGC2 | Function Assay | 50 μM | 48 h | DMSO | 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 | |
| ARPE-19 | Function Assay | 20 μM | 0.5 h | inhibits Apelin-induced phosphorylation of Erk and Akt | 24227918 | |
| 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 | |
| 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 | DMSO | 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 | DMSO | reverses BNF-induced cell cycle arrest | 24163404 |
| Caco-2 | Function Assay | 50 μM | 48h | DMSO | 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 | |
| MGC803 | Apoptosis Assay | 20 μM | 1 h | inhibits apoptosis induced by IFN-α and 5′-DFUR | 24027750 | |
| SGC7901 | Apoptosis Assay | 20 μM | 1 h | inhibits apoptosis induced by IFN-α and 5′-DFUR | 24027750 | |
| G292 | Apoptosis Assay | 30 μM | 2 h | restores capsaicin-induced cell death | 24012930 | |
| 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 | |
| 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 | DMSO | inhibits -induced CD11b expression | 23825585 |
| NB4 | Function Assay | 10 μM | 72 h | DMSO | inhibits -induced CD11b expression | 23825585 |
| EPOR/CR3 | Function Assay | 50 μM | 3 h | reduces EPO and/or IL-3-induced the tyrosine phosphorylation | 23820731 | |
| HUASMCs | Function Assay | 10 μM | 24 h | inhibits Ang II-induced ERK1/2 phosphorylation level | 23816468 | |
| 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 | |
| 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 | |
| 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 | DMSO | 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 | DMSO | upregulates the expression of HLA class I | 24244023 |
| TE5 | Function Assay | 50 μM | 48 h | DMSO | upregulates the expression of HLA class I | 24244023 |
| TE1 | Function Assay | 50 μM | 48 h | DMSO | upregulates the expression of HLA class I | 24244023 |
| TE3 | Function Assay | 50 μM | 48 h | DMSO | upregulates the expression of HLA class I | 24244023 |
| KYSE30 | Function Assay | 20/50/100 μM | 48 h | DMSO | inhibits p-Erk and wortmannin downregulated p-Akt in a dose-dependent manner | 24244023 |
| TE1 | Function Assay | 20/50/100 μM | 48 h | DMSO | inhibits p-Erk and wortmannin downregulated p-Akt in a dose-dependent manner | 24244023 |
| TE4 | Function Assay | 20/50/100 μM | 48 h | DMSO | 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 | |
| MC-3 | Apoptosis Assay | 10 μM | 24 h | potentiated MESC-induced apoptosis in cells | 24270523 | |
| 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 | |
| A549 | Function Assay | 30 μM | 0.5 h | DMSO | 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 | |
| A549 | Function Assay | 30 μM | 0.5 h | DMSO | inhibits the thrombin-induced IL-8/CXCL8-Luc activity | 24277696 |
| SW480 | Function Assay | 10 μM | 20 h | DMSO | suppresses the CRT activity | 24324366 |
| HEK 293 | Function Assay | 10 μM | 5 h | DMSO | inhibits Wnt-induced β-catenin/TCF4 activity and nuclear β-catenin accumulation | 24324366 |
| HEK 293 | Function Assay | 10 μM | 5 h | DMSO | 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 | DMSO | 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 | |
| HCT-15 | Function Assay | 1 h | attenuates PGE2-induced phosphorylation of Erk | 25431425 | ||
| 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 | |
| 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 | |
| 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 | |||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | |||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD 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 | |||
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 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 | ||
| MDA-MB-231 | Function assay | 50 uM | Downregulation of MMP9 in human MDA-MB-231 cells at 50 uM by Western blot analysis | 22926226 | ||
| Klik om meer experimentele gegevens over cellijnen te bekijken | ||||||
| Molecuulgewicht | 267.28 | Formule | C16H13NO3 |
Opslag (vanaf de datum van ontvangst) | |
|---|---|---|---|---|---|
| CAS-nr. | 167869-21-8 | SDF downloaden | Opslag van stamoplossingen |
|
|
| Synoniemen | N/A | Smiles | COC1=CC=CC(=C1N)C2=CC(=O)C3=CC=CC=C3O2 | ||
|
In vitro |
DMSO
: 46 mg/mL
(172.1 mM)
Water : Insoluble Ethanol : Insoluble |
|
In vivo |
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Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)
Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)
Berekeningsresultaten:
Werkconcentratie: mg/ml;
Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )
Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH2O, mengen en verhelderen.
Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.
Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.
| Kenmerken |
Does not inhibit c-Raf phosphorylated MEK1.
|
|---|---|
| Targets/IC50/Ki |
AhR
(Cell-free assay) 1 μM
MEK1
(Cell-free assay) 2 μM
|
| In vitro |
PD98059 remt ofwel basale MEK1 of een gedeeltelijk geactiveerde MEK geproduceerd door mutatie van serine op residuen 218 en 222 naar glutamaat (MEK-2E) met een IC50 van 2 μM. Deze verbinding remt de MAPK-homologen JNK en P38 niet. Het is zeer selectief tegen MEK, aangezien het een aantal andere kinase-activiteiten niet remt, waaronder Raf-kinase, cAMP-afhankelijk kinase, proteïne kinase C, v-Src, epidermale groeifactor (EGF) receptorkinase, insulinereceptorkinase, PDGF-receptorkinase en fosfatidylinositol 3-kinase. Deze remmer remt PDGF-gestimuleerde activering van MAPK en thymidine-incorporatie in 3T3-cellen met een IC50 van respectievelijk ~10 μM en ~7 μM. Het voorkomt krachtig de activering van MEK1 door Raf of MEK-kinase met een IC50 van 4 μM, en remt zwak de activering van MEK2 door Raf met een IC50 van 50 μM. Deze chemische stof remt de activering van MEK-homologen MKK4 en RK-kinase niet, die deelnemen aan stress- en interleukine-1-gestimuleerde kinasecascades in KB- en PC12-cellen, en de activering van p70 S6-kinase door insuline of epidermale groeifactor in Zwitserse 3T3-cellen. Het blokkeert volledig de zenuwgroeifactor (NGF)-geïnduceerde differentiatie van PC12-cellen zonder de cellevensvatbaarheid te beïnvloeden. Deze verbinding remt de proliferatie van RAW264.7-cellen in de kweek die RANKL bevat op een dosisafhankelijke manier, wat resulteert in een duidelijke afname van TRAP-positieve cellen. |
| Kinase Assay |
In vitro MEK-remmende activiteit
|
|
De incorporatie van 32P in myeline-basisch proteïne (MBP) wordt getest in aanwezigheid van glutathion S-transferase (GST) fusie-eiwitten die het 44-kDa MAPK (GST-MAPK) of het 45-kDa MEK (GST-MEK1) bevatten. Assays worden uitgevoerd in 50 μL van 50 mM Tris, pH 7.4/10 mM MgCl2/2 mM EGTA/10 μM [γ-32P]ATP met 10 μg GST-MEK1, 0.5 μg GST-MAPK en 40 μg MBP. Na incubatie bij 30°C gedurende 15 minuten worden de reacties gestopt door toevoeging van Laemmli SDS monsterbuffer. Gefosforyleerd MBP wordt gescheiden met SDS/10% PAGE.
|
|
| In vivo |
Behandeling van muizen 30 minuten voor focale cerebrale ischemie met PD98059 beschermt tegen schade, wat resulteert in een afname van het infarctvolume. Voorbehandeling met deze verbinding 30 minuten van tevoren en vervolgens samen met uurlijkse ceruleïne-injecties gedurende 3 uur verbetert significant ceruleïne-geïnduceerde acute pancreatitis op basis van pancreas natgewicht en histologie. Toediening van deze chemische stof (10 mg/kg) aan muizen 1 uur na carrageenan veroorzaakt een vermindering van alle gemeten ontstekingsparameters. |
Referenties |
|
| Methoden | Biomarkers | Afbeeldingen | 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 |
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Vraag 1:
How to formulate this inhibitor for i.p. injection?
Antwoord:
You can prepare the stock of this compound by the vehicle 30% PEG400/0.5% Tween80/5% Propylene glycol, 0.5% CMC.