solo para uso en investigación
Cat. No.S8078
| Dianas relacionadas | NF-κB HDAC Antioxidant ROS IκB/IKK AP-1 MALT NOD |
|---|---|
| Otros Nrf2 Inhibidores | ML385 Brusatol TBHQ Sulforaphane Oltipraz Bardoxolone (CDDO) 4-Octyl Itaconate (4-OI) KI696 CDDO-Im (RTA-403) Mangiferin |
| Líneas celulares | Tipo de ensayo | Concentración | Tiempo de incubación | Formulación | Descripción de la actividad | 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 | ||
| Haga clic para ver más datos experimentales de líneas celulares | ||||||
| Peso molecular | 505.69 | Fórmula | C32H43NO4 |
Almacenamiento (Desde la fecha de recepción) | |
|---|---|---|---|---|---|
| Nº CAS | 218600-53-4 | Descargar SDF | Almacenamiento de soluciones madre |
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| Sinónimos | 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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Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)
Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)
Resultados del cálculo:
Concentración de trabajo: mg/ml;
Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )
Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH2O, mezclar y clarificar.
Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.
Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.
| Características |
The only IKKβ inhibitor in clinical use for solid tumors, type 2 diabetes, and chronic kidney disease. An orally-available antioxidant inflammation modulator.
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|---|---|
| Targets/IC50/Ki |
IKK
(Cell-free assay) Ferroptosis
Nrf2
NF-κB
|
| In vitro |
El Bardoxolone Methyl exhibe potentes actividades inhibitorias contra la producción de óxido nítrico inducida por interferón-Ƴ en macrófagos de ratón con una IC50 de 0.1 nM. Este compuesto disminuye la viabilidad de las células leucémicas HL-60, KG-1 y NB4 con una IC50 de 0.4, 0.4 y 0.27 μM, respectivamente. Induce la proteína pro-apoptótica Bax, inhibe la activación de ERK1/2 y bloquea la fosforilación de Bcl-2, lo que contribuye a la inducción de la apoptosis. Este químico inhibe potentemente la NF-kappaB constitutiva e inducible activada por TNF, interleucina (IL)-1beta, éster de forbol, ácido okadaico, peróxido de hidrógeno, lipopolisacárido y humo de cigarrillo. |
| Ensayo de quinasa |
Ensayo de IKK
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Para determinar el efecto de CDDO-Me en la activación de IKK inducida por TNF, se analiza IKK. Brevemente, el complejo IKK de extractos de células enteras se precipitó con un anticuerpo contra IKKα e IKKβ y luego se trató con perlas de proteína A/G-Sepharose. Después de 2 horas, las perlas se lavan con tampón de lisis y luego se resuspenden en una mezcla de ensayo de quinasa que contiene 50 mmol/L HEPES (pH 7.4), 20 mmol/L MgCl2, 2 mmol/L DTT, 20 μCi [γ-32P]ATP, 10 μmol/L ATP no marcado y 2 μg del sustrato glutatión S-transferasa-IκBα (aminoácidos 1-54). Después de la incubación a 30°C durante 30 minutos, la reacción se termina hirviendo con tampón de muestra SDS durante 5 minutos. Finalmente, la proteína se resuelve en SDS-PAGE al 10%, el gel se seca y las bandas radiactivas se visualizan con un Storm820. Para determinar las cantidades totales de IKK-α e IKK-β en cada muestra, 50 μg de proteínas de células enteras se resuelven en SDS-PAGE al 7.5%, se transfieren electroforéticamente a una membrana de nitrocelulosa y luego se blotean con anticuerpos anti-IKK-α o anti-IKK-β.
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| In vivo |
El Bardoxolone Methyl (60 mg/kg) reduce el número, tamaño y gravedad de los tumores pulmonares in vivo. Este compuesto reduce significativamente la respuesta de citoquinas inflamatorias in vivo después del desafío con LPS, induce la expresión de la proteína HO-1 en el bazo y protege a los ratones contra una dosis letal de LPS. |
Referencias |
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| Métodos | Biomarcadores | Imágenes | 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 |
(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)
| Número NCT | Reclutamiento | Condiciones | Patrocinador/Colaboradores | Fecha de inicio | Fases |
|---|---|---|---|---|---|
| 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 |
Tel: +1-832-582-8158 Ext:3
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