Name: Birabresib (OTX015)
Brand: Selleck Chemicals
SKU: S7360
Rating: 5 (73 reviews)

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Lote: Pureza: 99.81%

99.81

Dianas relacionadas	HDAC JAK Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Histone Acetyltransferase
Otros BET Inhibidores	Pelabresib (CPI-0610) ZEN-3694 (BET-IN-19) Molibresib (I-BET-762) Mivebresib (ABBV-075) INCB054329 I-BET151 (GSK1210151A) Apabetalone (RVX-208) AZD5153 6-hydroxy-2-naphthoic acid CPI-203 I-BRD9

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad	PMID
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki=0.004μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD2 BD2 (349 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki=0.0054μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki=0.006μM.	26080064
MM1S	Antiproliferative assay		72 hrs	Antiproliferative activity against human MM1S cells after 72 hrs by CCK8 or SRB assay, IC50=0.0063μM.	31490070
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD3 BD1 (24 to 144 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki=0.0107μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki=0.0109μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD2 BD1 (72 to 205 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki=0.0166μM.	26080064
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, IC50=0.0166μM.	26080064
MV4-11	Antiproliferative assay		4 days	Antiproliferative activity against human MV4-11 cells assessed as cell growth inhibition after 4 days by CCK8 assay, IC50=0.0176μM.	31461688
MM1S	Antiproliferative assay		4 days	Antiproliferative activity against human MM1S cells assessed as cell growth inhibition after 4 days by CCK8 assay, IC50=0.0227μM.	31461688
Rosetta2 DE3	Function assay		30 mins	Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, IC50=0.0255μM.	26080064
THP1	Antiproliferative assay			Antiproliferative activity against human THP1 cells, IC50=0.033μM.	28939121
BL21(DE3)	Function assay		4 hrs	Displacement of 5-FITC labelled (+)-JQ1 from His6-tagged human BRD4 bromodomain 1 expressed in Escherichia coli BL21(DE3) )-codon plus-RIL cells incubated for 4 hrs in dark condition by fluorescence anisotropy binding assay, IC50=0.0343μM.	31490070
MV4-11	Antiproliferative assay		72 hrs	Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.0463μM.	32208600
TY82	Antiproliferative assay			Antiproliferative activity against human TY82 cells, IC50=0.067μM.	28939121
insect cells	Function assay			Inhibition of recombinant full length human N-terminal His6-tagged BRD4 (2 to 1362 residues) expressed in baculovirus infected insect cells using histone H4 peptide as substrate by alpha screen assay, IC50=0.092μM.	30529546
LNCAP	Antiproliferative assay			Antiproliferative activity against human LNCAP cells, IC50=0.1114μM.	29758518
Kasumi-1	Antiproliferative assay		72 hrs	Antiproliferative activity against human Kasumi-1 cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.135μM.	32208600
MM1S	Antiproliferative assay		72 hrs	Antiproliferative activity against human MM1S cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.137μM.	32208600
RS4:11	Antiproliferative assay		72 hrs	Antiproliferative activity against human RS4:11 cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.416μM.	32208600
MV4-11	Cell cycle assay	125 nM	24 hrs	Cell cycle arrest in human MV4-11 cells assessed as increase in accumulation at G1-phase at 125 nM measured after 24 hrs by propidium iodide staining based flow cytometry	32208600
MV4-11	Function assay	500 nM	6 to 24 hrs	Inhibition of BRD4 in human MV4-11 cells assessed as reduction in c-Myc expression at 500 nM measured after 6 to 24 hrs by Western blot analysis	32208600
MV4-11	Function assay	31.25 to 125 nM	6 hrs	Inhibition of BRD4 in human MV4-11 cells assessed as reduction in c-Myc mRNA level at 31.25 to 125 nM measured after 6 hrs by SYBR green dye based RT-qPCR analysis	32208600
MV4-11	Function assay	31.25 to 125 nM	6 hrs	Inhibition of BRD4 in human MV4-11 cells assessed as reduction in BCL2 mRNA level at 31.25 to 125 nM measured after 6 hrs by SYBR green dye based RT-qPCR analysis	32208600
MV4-11	Function assay	31.25 to 125 nM	6 hrs	Inhibition of BRD4 in human MV4-11 cells assessed as reduction in CDK6 mRNA level at 31.25 to 125 nM measured after 6 hrs by SYBR green dye based RT-qPCR analysis	32208600
TY82	Antiproliferative assay		72 hrs	Antiproliferative activity against human TY82 cells after 72 hrs by CCK8 or SRB assay	31490070
MV4-11	Function assay	10 to 100 nM	24 hrs	Inhibition of BRD4 in human MV4-11 cells assessed as reduction in c-Myc mRNA level at 10 to 100 nM after 24 hrs by real time qPCR analysis	31490070
MV4-11	Antiproliferative assay		72 hrs	Antiproliferative activity against human MV4-11 cells after 72 hrs by CCK8 or SRB assay	31490070
MV4-11	Apoptosis assay		24 hrs	Induction of apoptosis in human MV4-11 cells after 24 hrs by Annexin V staining based assay	31490070
RKO	Cell cycle assay	100 nM	24 hrs	Induction of cell cycle arrest in human RKO cells assessed as increase in accumulation at G1 phase at 100 nM after 24 hrs by propidium iodide staining based flow cytometric analysis	31490070
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Información química, almacenamiento y estabilidad

Peso molecular	491.99	Fórmula	C₂₅H₂₂ClN₅O₂S	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	202590-98-5	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	MK 8628			Smiles	CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)NC4=CC=C(C=C4)O)C5=CC=C(C=C5)Cl)C

Solubilidad

In vitro
Lote:

DMSO : 98 mg/mL (199.19 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 11 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

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.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

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.

Mecanismo de acción

Características	Orally bioavailable BRD2/3/4-selective inhibitor that has been tested in Phase I clinical trials for treatment of Haematological Malignancies.
Targets/IC₅₀/Ki	BRDs (Cell-free assay) 10-19 nM(EC50)
In vitro	Birabresib (OTX015) inhibe la unión de BRD2, BRD3 y BRD4 a AcH4 con una IC50 que oscila entre 92 y 112 nM, e inhibe el crecimiento de una variedad de líneas celulares de cáncer humano con una GI50 que oscila entre 60 y 200 nM. Resulta en una rápida regulación a la baja de la expresión de c-MYC y muestra efectos antiproliferativos sinérgicos en combinación con inhibidores de ALK en líneas celulares de ALCL ALKpos.
Ensayo de quinasa	Ensayo TR-FRET
Ensayo de quinasa	Para evaluar la unión de Birabresib (OTX015) a BRD2, BRD3 y BRD4, se incuban durante 0,2 a 2 h a temperatura ambiente lisados de células CHO que expresan BRD (de células CHO transfectadas con plásmidos de expresión para BRD2, BRD3 o BRD4 con etiqueta Flag o solo el vector), anticuerpo anti-Flag conjugado con europio, estreptavidina conjugada con XL-665 y biotina. La fluorescencia se mide mediante TR-FRET utilizando un lector multietiqueta EnVision 2103 y la EC50 para la unión se calcula mediante regresión no lineal utilizando PRISM versión 5.02.
In vivo	Birabresib (OTX015) inhibe significativamente el crecimiento de tumores de carcinoma de línea media Ty82 BRD-NUT en ratones desnudos en un 79% a 100 mg/kg qd y en un 61% a 10 mg/kg bid, respectivamente, cuando se administra por vía oral (p.o.).
Referencias	[1] http://mct.aacrjournals.org/content/12/11_Supplement/C244.short [2] http://mct.aacrjournals.org/content/12/11_Supplement/A219.short

Aplicaciones

Métodos	Biomarcadores	Imágenes	PMID
Western blot	BRD4 c-Myc JAK2 / p-STAT5 / STAT5 / p-STAT3 / c-Myc / PIM1 / CDK6 / HEXIM1 / p27 / p21 / Bcl-xL / γH2AX ZO-1 / Vimentin		26051217
Immunofluorescence	BRD4 Vimentin		28042144

Información del ensayo clínico

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT02698176	Terminated	NUT Midline Carcinoma (NMC)\|Triple Negative Breast Cancer (TNBC)\|Non-small Cell Lung Cancer (NSCLC)\|Castration-resistant Prostate Cancer (CRPC)	Merck Sharp & Dohme LLC	May 4 2016	Phase 1
NCT02698189	Terminated	AML Including AML de Novo and AML Secondary to MDS\|DLBCL	Merck Sharp & Dohme LLC	May 19 2016	Phase 1
NCT02296476	Terminated	Glioblastoma Multiforme	Oncoethix GmbH a subsidiary of Merck & Co. Inc. (Rahway New Jersey USA)	October 29 2014	Phase 2
NCT02259114	Completed	NUT Midline Carcinoma\|Triple Negative Breast Cancer\|Non-small Cell Lung Cancer With Rearranged ALK Gene/Fusion Protein or KRAS Mutation\|Castrate-resistant Prostate Cancer\|CRPC\|Pancreatic Ductal Adenocarcinoma	Oncoethix GmbH a subsidiary of Merck & Co. Inc. (Rahway New Jersey USA)	October 23 2014	Phase 1
NCT01713582	Completed	Acute Myeloid Leukemia\|Diffuse Large B-cell Lymphoma\|Acute Lymphoblastic Leukemia\|Multiple Myeloma	Oncoethix GmbH a subsidiary of Merck & Co. Inc. (Rahway New Jersey USA)	December 14 2012	Phase 1

Soporte técnico

Instrucciones de manipulación

Tel: +1-832-582-8158 Ext:3

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C5=C4/X	C5:	LOG(C5):
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Birabresib (OTX015) BET inhibidor

Estructura química

Peso molecular: 491.99