Home Epigenetics Epigenetic Reader Domain inhibitor - NSD inhibitor Birabresib (OTX015) For research use only.

Birabresib (OTX015)

Synonyms: MK 8628

Birabresib (OTX015, MK 8628) is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. Birabresib inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes.

Birabresib (OTX015) Chemical Structure

Birabresib (OTX015) Chemical Structure

CAS No. 202590-98-5

Purity & Quality Control

Birabresib (OTX015) Related Products

Signaling Pathway

Epigenetic Reader Domain Signaling Pathways

Epigenetic Reader Domain Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description 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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Biological Activity

Description Birabresib (OTX015, MK 8628) is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. Birabresib inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes.
Features Orally bioavailable BRD2/3/4-selective inhibitor that has been tested in Phase I clinical trials for treatment of Haematological Malignancies.
Targets
BRDs [1]
(Cell-free assay)
10-19 nM(EC50)
In vitro
In vitro OTX015 inhibits the binding of BRD2, BRD3, and BRD4 to AcH4 with IC50 ranging from 92 to 112 nM, and inhibits the growth of a variety of human cancer cell lines with GI50 ranging from 60 to 200 nM. [1] OTX015 results in rapid down-regulation of c-MYC expression, and show the synergistic anti-proliferative effects in combination with ALK inhibitors in ALKpos ALCL cell lines. [2]
Kinase Assay TR-FRET Assay [1]
To assess binding of OTX015 to BRD2, BRD3, and BRD4, BRD-expressing CHO cell lysate (from CHO cells transfected with expression plasmids for Flag-tagged BRD2, BRD3, or BRD4 or vector alone), europium-conjugated anti-Flag antibody, XL-665-conjugated streptavidin, and biotinylated OTX015 are incubated at room temperature for 0.2 to 2 h. Fluorescence is measured by TR-FRET using an EnVision 2103 Multilabel Reader and EC50 for binding is calculated by nonlinear regression using PRISM version 5.02.
Cell Research Cell lines Human tumor cells
Concentrations ~2 μM
Incubation Time 72 hours
Method

Effects of OTX015 on cancer cell proliferation are evaluated by incubating human tumor cells for 72 h with increasing concentrations of OTX015 and assessing proliferation using a tetrazolium salt (WST-8)-based colorimetric assay.
Experimental Result Images Methods Biomarkers Images PMID
Western blot ZO-1 / Vimentin JAK2 / p-STAT5 / STAT5 / p-STAT3 / c-Myc / PIM1 / CDK6 / HEXIM1 / p27 / p21 / Bcl-xL / γH2AX c-Myc BRD4 27980063
Immunofluorescence Vimentin BRD4 27980063
In Vivo
In vivo OTX015 (p.o.) significantly inhibits the growth of Ty82 BRD-NUT midline carcinoma tumors in nude mice by 79% at 100 mg/kg qd and 61% at 10 mg/kg bid, respectively. [1]
Animal Research Animal Models BLAB/c-nu/nu mice bearing established Ty82 BRD-NUT midline carcinoma xenografts.
Dosages ~100 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date 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

Chemical Information & Solubility

Molecular Weight 491.99 Formula

C25H22ClN5O2S
CAS No. 202590-98-5 SDF Download Birabresib (OTX015) SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 98 mg/mL ( (199.19 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 98 mg/mL

Water : Insoluble


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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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