pour la recherche uniquement
Réf. CatalogueS8078
| Cibles apparentées | NF-κB HDAC Antioxidant ROS IκB/IKK AP-1 MALT NOD |
|---|---|
| Autre Nrf2 Inhibiteurs | ML385 TBHQ Sulforaphane Brusatol Oltipraz Bardoxolone (CDDO) 4-Octyl Itaconate (4-OI) KI696 Mangiferin CDDO-Im (RTA-403) |
| Lignées cellulaires | Type d'essai | Concentration | Temps d'incubation | Formulation | Description de l'activité | PMID |
|---|---|---|---|---|---|---|
| MCF-7 | Function assay | Inhibitory concentration against proliferation of MCF-7 (ER Positive) breast cancer cells, IC50=0.05μM | 15369396 | |||
| BMDM | Cytotoxicity assay | 24 hrs | Cytotoxicity against C57BL/6 mouse BMDM cells assessed as LDH release after 24 hrs, MNTD=0.5μM | 22533790 | ||
| BMDM | Antiinflammatory assay | 0.5 uM | 1 hr | Antiinflammatory activity in C57BL/6 mouse BMDM cells assessed as inhibition of LPS-stimulated TNFalpha production at 0.5 uM pretreated for 1 hr before LPS challenge after 8 to 24 hrs by immunoassay | 22533790 | |
| PANC1343 | Antiproliferative assay | 300 to 1000 nM | 72 hrs | Antiproliferative activity against mouse PANC1343 cells at 300 to 1000 nM after 72 hrs by MTT assay | 24388806 | |
| RAW264.7 | Antioxidant assay | 100 nM | 18 hrs | Antioxidant activity in mouse RAW264.7 cells assessed as inhibition of tBHP-induced ROS production at 100 nM pretreated for 18 hrs before challenge measured after 15 mins by H2DCFA-based flow cytometry | 24388806 | |
| HepG2 | Cytotoxicity assay | 48 hrs | Cytotoxicity against human HepG2 cells after 48 hrs by MTT assay, IC50=4.99μM | 24685545 | ||
| B16F10 | Cytotoxicity assay | 48 hrs | Cytotoxicity against mouse B16F10 cells after 48 hrs by MTT assay, IC50=5.85μM | 24685545 | ||
| CCD-841-CoN | Antiproliferative assay | 72 hrs | Antiproliferative activity against human CCD-841-CoN cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.316μM | 25675144 | ||
| HCT8 | Antiproliferative assay | 72 hrs | Antiproliferative activity against 5-FU resistant human HCT8 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.363μM | 25675144 | ||
| HCT8 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HCT8 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay, IC50=0.399μM | 25675144 | ||
| HCT8 | Function assay | 1 uM | 24 hrs | Inhibition of HIF-1alpha protein expression in human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method | 25675144 | |
| HCT8 | Function assay | 1 uM | 24 hrs | Inhibition of HIF-1alpha protein expression in FU-resistant human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method | 25675144 | |
| HCT8 | Function assay | 1 uM | 24 hrs | Inhibition of STAT3 protein phosphorylation in human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method | 25675144 | |
| HCT8 | Function assay | 1 uM | 24 hrs | Inhibition of STAT3 protein phosphorylation in FU-resistant human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method | 25675144 | |
| HCT8 | Function assay | 1 uM | 24 hrs | Inhibition of AKT protein phosphorylation in human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method | 25675144 | |
| HCT8 | Function assay | 1 uM | 24 hrs | Inhibition of AKT protein phosphorylation in FU-resistant human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method | 25675144 | |
| HCT8 | Function assay | 1 uM | 24 hrs | Inhibition of ERK protein phosphorylation in human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method | 25675144 | |
| HCT8 | Function assay | 1 uM | 24 hrs | Inhibition of ERK protein phosphorylation in FU-resistant human HCT8 cells at 1 uM incubated for 24 hrs by Western blotting method | 25675144 | |
| HCT8 | Antiproliferative assay | 1 uM | 72 hrs | Antiproliferative activity against human HCT8 cells assessed as inhibition of cell proliferation at 1 uM after 72 hrs by MTT assay | 25675144 | |
| HCT8 | Antiproliferative assay | 1 uM | 72 hrs | Antiproliferative activity against 5-FU resistant human HCT8 cells assessed as inhibition of cell proliferation at 1 uM after 72 hrs by MTT assay | 25675144 | |
| BEAS2B | Function assay | 10 uM | 6 hrs | Activation of Nrf2 in human BEAS2B cells assessed as increase in HO1 gene expression at 10 uM incubated for 6 hrs by qPCR method | 26278028 | |
| H42E | Function assay | 24 hrs | Induction of NRF2 activation in rat H42E cells expressing ARE8L assessed as reporter transgene activity after 24 hrs by luminescence assay, CD=0.0005μM | 26908173 | ||
| H42E | Cytotoxicity assay | 24 hrs | Cytotoxicity against rat H42E cells expressing ARE8L assessed as cellular ATP level after 24 hrs by Celltiter-Glo luminescent cell viability assay, IC50=1.4μM | 26908173 | ||
| H42E | Function assay | 0.01 to 30 nM | 1 hr | Stabilization of NRF2 in rat H42E cells expressing ARE8L at 0.01 to 30 nM after 1 hr by Western blot analysis | 26908173 | |
| NHBE | Cytoprotective assay | 0.001 to 0.1 uM | 18 hrs | Cytoprotective activity in NHBE cells assessed as inhibition of tBHP-induced GSH depletion at 0.001 to 0.1 uM preincubated for 18 hrs followed by tBHP addition for 4 hrs by thiostar dye based fluorescence assay | 27031670 | |
| NHBE | Function assay | 100 nM | 24 hrs | Inhibition of KEAP1/NRF2 interaction in NHBE cells assessed as increase in GCLM mRNA expression at 100 nM incubated for 24 hrs in presence of non targeting siRNA by qRT-PCR method | 27031670 | |
| NHBE | Function assay | 100 nM | 24 hrs | Inhibition of KEAP1/NRF2 interaction in NHBE cells assessed as increase in NQO1 mRNA expression at 100 nM incubated for 24 hrs in presence of non targeting siRNA by qRT-PCR method | 27031670 | |
| NHBE | Function assay | 100 nM | 48 hrs | Inhibition of KEAP1/NRF2 interaction in NHBE cells assessed as induction of NQO1 specific activity at 100 nM incubated for 48 hrs in presence of non targeting siRNA by MTT reduction assay | 27031670 | |
| HaCaT-ARE-luc | Function assay | 6 hrs | Activation of Nrf2 (unknown origin) expressed in human HaCaT-ARE-luc cells after 6 hrs by luciferase reporter gene assay, EC50=0.06μM | 28753294 | ||
| NIH/3T3 | Function assay | 6 hrs | Inhibition of TNF-alpha stimulated NF-kappaB (unknown origin) expressed in mouse NIH/3T3 cells after 6 hrs by luciferase reporter gene assay, IC50=1.2μM | 28753294 | ||
| HeLa | Function assay | 6 hrs | Inhibition of IFN-gamma stimulated STAT3 (unknown origin) expressed in human HeLa cells after 6 hrs by luciferase reporter gene assay, IC50=2.38μM | 28753294 | ||
| RAW264.7 | Anti-inflammatory assay | Anti-inflammatory activity in mouse RAW264.7 cells assessed as inhibition of nitric oxide production, IC50=4μM | 28754470 | |||
| HEK293 | Cytotoxicity assay | 24 hrs | Cytotoxicity against HEK293 cells assessed as reduction in cell viability after 24 hrs by MTT assay, IC50=2.2μM | 28994286 | ||
| H9c2 | Cytotoxicity assay | 24 hrs | Cytotoxicity against rat H9c2 cells assessed as reduction in cell viability after 24 hrs by MTT assay, IC50=5.2μM | 28994286 | ||
| HEK293 | Function assay | 200 to 1000 nM | 24 hrs | Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as TNFalpha-induced NFkappaB activation at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by NFkappaB-driven luciferase reporter gene assay | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 24 hrs | Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of iNOS mRNA expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by quantitative RT-PCR an | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 24 hrs | Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of COX2 mRNA expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by quantitative RT-PCR an | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 24 hrs | Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of MCP1 mRNA expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by quantitative RT-PCR an | 28994286 | |
| intraglomerular mesangial cells | Function assay | 0.65 mg/kg | 12 weeks | Renoprotective activity in db/db mouse assessed as increase in number of intraglomerular mesangial cells at 0.65 mg/kg, ip administered trice per week for 12 consecutive weeks measured at 11 weeks post dose by H/E-staining based microscopic analysis | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 24 hrs | Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of COX2 protein expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by Western blot method | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 24 hrs | Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of iNOS protein expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by Western blot method | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 24 hrs | Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as mitigation of TNFalpha-induced increase in ratio of nuclear to cytosolic p65 at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by Western blot | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 24 hrs | Inhibition of IKKbeta (unknown origin) transfected in HEK293 cells assessed as reduction in TNFalpha-induced upregulation of MCP1 protein expression at 200 to 1000 nM administered 6 hrs after TNFalpha stimulation measured for 24 hrs by Western blot method | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 48 hrs | Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as upregulation of HO-1 mRNA expression at 200 to 1000 nM after 48 hrs by quantitative RT-PCR analysis | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 48 hrs | Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as upregulation of NQO1 mRNA expression at 200 to 1000 nM after 48 hrs by quantitative RT-PCR analysis | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 48 hrs | Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as activation of Nrf2 at 200 to 1000 nM after 48 hrs by ARE-driven luciferase reporter gene assay | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 48 hrs | Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as increase in nuclear to cytosolic Nfr2 ratio at 200 to 1000 nM after 48 hrs by Western blot analysis | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 48 hrs | Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as increase in cytosolic HO-1 levels at 200 to 1000 nM after 48 hrs by Western blot analysis | 28994286 | |
| HEK293 | Function assay | 200 to 1000 nM | 48 hrs | Inhibition of Keap1/Nrf2 (unknown origin) interaction transfected in HEK293 cells assessed as increase in cytosolic NQO1 levels at 200 to 1000 nM after 48 hrs by Western blot analysis | 28994286 | |
| A549/TR | Antiproliferative assay | 72 hrs | Antiproliferative activity against human A549/TR cells after 72 hrs by MTT assay, IC50=1.703μM | 29501947 | ||
| A549 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50=2.074μM | 29501947 | ||
| A549/TR | Function assay | 2.4 to 9.6 uM | 24 hrs | Induction of ROS generation in human A549/TR cells at 2.4 to 9.6 uM after 24 hrs by DCFH-DA dye-based flow cytometric analysis | 29501947 | |
| A549/TR | Function assay | 4.8 uM | 24 hrs | Downregulation of Lon expression in human A549/TR cells at 4.8 uM after 24 hrs by Western blot analysis | 29501947 | |
| HCT116 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50=0.00025μM | 30429953 | ||
| HT-29 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HT-29 cells after 72 hrs by SRB assay, IC50=0.28μM | 30429953 | ||
| HCT8 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HCT8 cells after 72 hrs by SRB assay, IC50=0.29μM | 30429953 | ||
| HCT116 | Function assay | 8 hrs | Inhibition of Bmi1 protein expression in human HCT116 cells after 8 hrs by Western blot analysis | 30429953 | ||
| BEAS2B | Function assay | 48 hrs | Activation of Keap1/Cul3/Nrf2 in human BEAS2B cells assessed as increase in NQO1 levels measured after 48 hrs, EC50=0.00871μM | 30626555 | ||
| HepG2 | Cytotoxicity assay | 48 hrs | Cytotoxicity against human HepG2 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay, IC50=0.26μM | 31051401 | ||
| MCF7 | Cytotoxicity assay | 48 hrs | Cytotoxicity against human MCF7 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay, IC50=0.35μM | 31051401 | ||
| A549 | Cytotoxicity assay | 48 hrs | Cytotoxicity against human A549 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay, IC50=0.36μM | 31051401 | ||
| A549 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human A549 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay, IC50=0.52μM | 31725288 | ||
| HepG2 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human HepG2 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay, IC50=0.52μM | 31725288 | ||
| HOS | Antiproliferative assay | 48 hrs | Antiproliferative activity against human HOS cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay, IC50=0.66μM | 31725288 | ||
| MCF7 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human MCF7 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay, IC50=0.85μM | 31725288 | ||
| HEK293FT | Function assay | 24 hrs | Inhibition of mouse GOAT expressed in HEK293FT cells co-expressing pre-proghrelin assessed as reduction in ghrelin octanoylation incubated for 24 hrs by ELISA, IC50=0.035μM | ChEMBL | ||
| Cliquez pour voir plus de données expérimentales sur la lignée cellulaire | ||||||
| Poids moléculaire | 505.69 | Formule | C32H43NO4 |
Stockage (À compter de la date de réception) | |
|---|---|---|---|---|---|
| N° CAS | 218600-53-4 | Télécharger le SDF | Stockage des solutions mères |
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| Synonymes | RTA 402, TP-155, NSC 713200, CDDO Methyl Ester, CDDO-Me | Smiles | CC1(CCC2(CCC3(C(C2C1)C(=O)C=C4C3(CCC5C4(C=C(C(=O)C5(C)C)C#N)C)C)C)C(=O)OC)C | ||
|
In vitro |
DMSO
: 26 mg/mL
(51.41 mM)
Water : Insoluble Ethanol : Insoluble |
|
In vivo |
|||||
Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant l'expérience)
Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter d'abord s'il n'y a pas de formulation in vivo dans la section Solubilité.)
Résultats du calcul :
Concentration de travail : mg/ml;
Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter d'abord si la concentration dépasse la solubilité du DMSO du lot de médicament. )
Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH2O, mélanger et clarifier.
Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.
Note : 1. Veuillez vous assurer que le liquide est clair avant d'ajouter le solvant suivant.
2. Assurez-vous d'ajouter le(s) solvant(s) dans l'ordre. Vous devez vous assurer que la solution obtenue, lors de l'ajout précédent, est une solution claire avant de procéder à l'ajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.
| Caractéristiques |
The only IKKβ inhibitor in clinical use for solid tumors, type 2 diabetes, and chronic kidney disease. An orally-available antioxidant inflammation modulator.
|
|---|---|
| Targets/IC50/Ki |
IKK
(Cell-free assay) Ferroptosis
Nrf2
NF-κB
|
| In vitro |
Le Bardoxolone Methyl présente de puissantes activités inhibitrices contre la production d'oxyde nitrique induite par l'interféron-Ƴ dans les macrophages de souris avec une IC50 de 0,1 nM. Ce composé diminue la viabilité des cellules leucémiques HL-60, KG-1 et NB4 avec des IC50 de 0,4, 0,4 et 0,27 μM, respectivement. Il induit la protéine pro-apoptotique Bax, inhibe l'activation d'ERK1/2 et bloque la phosphorylation de Bcl-2, ce qui contribue à l'induction de l'apoptose. Ce produit chimique inhibe puissamment l'activation constitutive et inductible de NF-kappaB activée par le TNF, l'interleukine (IL)-1beta, l'ester de phorbol, l'acide okadaïque, le peroxyde d'hydrogène, le lipopolysaccharide et la fumée de cigarette. |
| Essai kinase |
Test IKK
|
|
Pour déterminer l'effet du CDDO-Me sur l'activation de l'IKK induite par le TNF, l'IKK est analysée. En bref, le complexe IKK des extraits cellulaires entiers a été précipité avec un anticorps contre IKKα et IKKβ, puis traité avec des billes de Protéine A/G-Sépharose. Après 2 heures, les billes sont lavées avec un tampon de lyse puis resuspendues dans un mélange de dosage de kinase contenant 50 mmol/L HEPES (pH 7,4), 20 mmol/L MgCl2, 2 mmol/L DTT, 20 μCi [γ-32P]ATP, 10 μmol/L ATP non marqué et 2 μg du substrat glutathion S-transférase-IκBα (acides aminés 1-54). Après incubation à 30°C pendant 30 minutes, la réaction est arrêtée par ébullition avec un tampon d'échantillon SDS pendant 5 minutes. Enfin, la protéine est résolue sur un SDS-PAGE à 10 %, le gel est séché et les bandes radioactives sont visualisées avec un Storm820. Pour déterminer les quantités totales d'IKK-α et d'IKK-β dans chaque échantillon, 50 μg de protéines cellulaires entières sont résolues sur un SDS-PAGE à 7,5 %, transférées électrophorétiquement sur une membrane de nitrocellulose, puis immunobuvardées avec un anticorps anti-IKK-α ou anti-IKK-β.
|
|
| In vivo |
Le Bardoxolone Methyl (60 mg/kg) réduit le nombre, la taille et la gravité des tumeurs pulmonaires in vivo. Ce composé réduit significativement la réponse cytokinique inflammatoire in vivo suite à une exposition au LPS, induit l'expression de la protéine HO-1 dans la rate et protège les souris contre une dose létale de LPS. |
Références |
|
| Méthodes | Biomarqueurs | Images | PMID |
|---|---|---|---|
| Western blot | p-IκBα / IκBα Bcl-xl / Bcl-2 / Bax / Cleaved caspase / Cytochrome C / PARP / Cleaved PARP p-PI3K / PI3K / p-AMPK / AMPK / p-p38 MAPK / p38 MAPK / p-AKT / AKT / p-mTOR / mTOR PTEN / PP2A / PHLPP1 |
|
25897966 |
| Immunofluorescence | PDI / SDHA c-PARP / Cytochrome C / COX IV |
|
26053096 |
| Growth inhibition assay | Cell viability |
|
25733817 |
(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)
| Numéro NCT | Recrutement | Conditions | Promoteur/Collaborateurs | Date de début | Phases |
|---|---|---|---|---|---|
| NCT02316821 | Completed | Chronic Kidney Disease|Type 2 Diabetes |
Kyowa Kirin Co. Ltd. |
December 2014 | Phase 2 |
| NCT02036970 | Completed | Pulmonary Arterial Hypertension|Pulmonary Hypertension|Interstitial Lung Disease|Idiopathic Interstitial Pneumonia|Idiopathic Pulmonary Fibrosis|Sarcoidosis|Respiratory Bronchiolitis Associated Interstitial Lung Disease|Desquamative Interstitial Pneumonia|Cryptogenic Organizing Pneumonia|Acute Interstitial Pneumonitis|Idiopathic Lymphoid Interstitial Pneumonia|Idiopathic Pleuroparenchymal Fibroelastosis |
Reata a wholly owned subsidiary of Biogen|Biogen |
May 31 2014 | Phase 2 |
| NCT01598363 | Completed | Healthy Volunteers |
Reata a wholly owned subsidiary of Biogen|Biogen |
June 30 2012 | Phase 1 |
| NCT01551446 | Withdrawn | Renal Insufficiency Chronic|Diabetes Mellitus Type 2 |
Reata a wholly owned subsidiary of Biogen|Biogen |
April 30 2012 | Phase 1 |
| NCT01503866 | Completed | Healthy |
Reata a wholly owned subsidiary of Biogen|Biogen |
December 1 2011 | Phase 1 |