solo per uso di ricerca
N. Cat.S8078
| Target correlati | NF-κB HDAC Antioxidant ROS IκB/IKK AP-1 MALT NOD |
|---|---|
| Altro Nrf2 Inibitori | ML385 Brusatol TBHQ Sulforaphane Oltipraz Bardoxolone (CDDO) 4-Octyl Itaconate (4-OI) KI696 CDDO-Im (RTA-403) Mangiferin |
| Linee cellulari | Tipo di saggio | Concentrazione | Tempo di incubazione | Formulazione | Descrizione dellattività | 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 | ||
| Clicca per visualizzare più dati sperimentali sulle linee cellulari | ||||||
| Peso molecolare | 505.69 | Formula | C32H43NO4 |
Conservazione (Dalla data di ricezione) | |
|---|---|---|---|---|---|
| N. CAS | 218600-53-4 | Scarica SDF | Conservazione delle soluzioni stock |
|
|
| Sinonimi | 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 |
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Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante lesperimento)
Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non cè una formulazione in vivo nella sezione Solubilità.)
Risultati del calcolo:
Concentrazione di lavoro: mg/ml;
Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )
Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH2O, mescolare e chiarire.
Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.
Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nellaggiunta precedente, sia una soluzione limpida prima di procedere allaggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno dacqua calda possono essere utilizzati per facilitare la dissoluzione.
| Caratteristiche |
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 |
Il Bardoxolone Methyl mostra potenti attività inibitorie contro la produzione di ossido nitrico indotta dall'interferone-Ƴ nei macrofagi di topo con un IC50 di 0,1 nM. Questo composto diminuisce la vitalità delle cellule leucemiche HL-60, KG-1 e NB4 con IC50 di 0,4, 0,4 e 0,27 μM, rispettivamente. Induce la proteina pro-apoptotica Bax, inibisce l'attivazione di ERK1/2 e blocca la fosforilazione di Bcl-2, il che contribuisce all'induzione dell'apoptosi. Questa sostanza chimica inibisce potentemente sia la NF-kappaB costitutiva che quella inducibile attivata da TNF, interleuchina (IL)-1beta, estere di forbolo, acido okadaico, perossido di idrogeno, lipopolisaccaride e fumo di sigaretta. |
| Saggio chinasico |
Saggio IKK
|
|
Per determinare l'effetto di CDDO-Me sull'attivazione di IKK indotta da TNF, si analizza l'IKK. In breve, il complesso IKK dagli estratti di cellule intere è stato precipitato con un anticorpo contro IKKα e IKKβ e quindi trattato con perline di proteina A/G-Sepharose. Dopo 2 ore, le perline vengono lavate con tampone di lisi e quindi risospese in una miscela di saggio della chinasi contenente 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 marcato e 2 μg del substrato glutatione S-transferasi-IκBα (amminoacidi 1-54). Dopo incubazione a 30°C per 30 minuti, la reazione viene terminata per ebollizione con tampone di campionamento SDS per 5 minuti. Infine, la proteina viene risolta su SDS-PAGE al 10%, il gel viene essiccato e le bande radioattive vengono visualizzate con uno Storm820. Per determinare le quantità totali di IKK-α e IKK-β in ciascun campione, 50 μg di proteine di cellule intere vengono risolte su SDS-PAGE al 7,5%, elettrotrasferite su una membrana di nitrocellulosa e quindi blottate con anticorpo anti-IKK-α o anti-IKK-β.
|
|
| In vivo |
Il Bardoxolone Methyl (60 mg/kg) riduce il numero, le dimensioni e la gravità dei tumori polmonari in vivo. Questo composto riduce significativamente la risposta infiammatoria delle citochine in vivo dopo la stimolazione con LPS, induce l'espressione della proteina HO-1 nella milza e protegge i topi da una dose letale di LPS. |
Riferimenti |
|
| Metodi | Biomarcatori | Immagini | 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 |
(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)
| Numero NCT | Reclutamento | Condizioni | Sponsor/Collaboratori | Data di inizio | Fasi |
|---|---|---|---|---|---|
| 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 |
Istruzioni per la manipolazione
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