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

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Contrôle Qualité

Lot : Pureté : 99.81%

99.81

Cibles apparentées	HDAC JAK Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Histone Acetyltransferase
Autre BET Inhibiteurs	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

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	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
Cliquez pour voir plus de données expérimentales sur la lignée cellulaire

Informations chimiques, stockage et stabilité

Poids moléculaire	491.99	Formule	C₂₅H₂₂ClN₅O₂S	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	202590-98-5	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	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

Solubilité

In vitro
Lot:

DMSO : 98 mg/mL (199.19 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 11 mg/mL

Water : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant lexpérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

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 dabord 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 dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue, lors de lajout précédent, est une solution claire avant de procéder à lajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Caractéristiques	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 liaison de BRD2, BRD3 et BRD4 à AcH4 avec une IC50 allant de 92 à 112 nM, et inhibe la croissance d'une variété de lignées cellulaires cancéreuses humaines avec une GI50 allant de 60 à 200 nM. Il entraîne une régulation rapide à la baisse de l'expression de c-MYC et montre des effets antiprolifératifs synergiques en combinaison avec des inhibiteurs d'ALK dans les lignées cellulaires ALCL ALKpos.
Essai kinase	Essai TR-FRET
Essai kinase	Pour évaluer la liaison de Birabresib (OTX015) à BRD2, BRD3 et BRD4, le lysat cellulaire de CHO exprimant BRD (provenant de cellules CHO transfectées avec des plasmides d'expression pour BRD2, BRD3 ou BRD4 marqués par Flag ou un vecteur seul), un anticorps anti-Flag conjugué à l'europium, de la streptavidine conjuguée à XL-665 et de la biotine sont incubés à température ambiante pendant 0,2 à 2 h. La fluorescence est mesurée par TR-FRET à l'aide d'un lecteur multilabel EnVision 2103 et l'EC50 pour la liaison est calculée par régression non linéaire à l'aide de PRISM version 5.02.
In vivo	Birabresib (OTX015) inhibe significativement la croissance des tumeurs de carcinome de la ligne médiane Ty82 BRD-NUT chez les souris nues de 79% à 100 mg/kg qd et de 61% à 10 mg/kg bid, respectivement, lorsqu'il est administré par voie orale (p.o.).
Références	[1] http://mct.aacrjournals.org/content/12/11_Supplement/C244.short [2] http://mct.aacrjournals.org/content/12/11_Supplement/A219.short

Applications

Méthodes	Biomarqueurs	Images	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

Informations sur lessai clinique

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
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

Support technique

Instructions de manipulation

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

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C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
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Birabresib (OTX015) BET inhibiteur

Structure chimique

Poids moléculaire: 491.99