Birabresib (OTX015)

Catalog No.S7360 Batch:S736007

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Technical Data

Formula

C25H22ClN5O2S
Molecular Weight 491.99 CAS No. 202590-98-5
Solubility (25°C)* In vitro DMSO 98 mg/mL (199.19 mM)
Ethanol 11 mg/mL (22.35 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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.
Targets
BRDs [1]
(Cell-free assay)
10-19 nM(EC50)
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]
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]
Features Orally bioavailable BRD2/3/4-selective inhibitor that has been tested in Phase I clinical trials for treatment of Haematological Malignancies.

Protocol (from reference)

Kinase Assay:

[1]
  • 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 Assay:

[1]
  • 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.
Animal Study:

[1]
  • Animal Models

    BLAB/c-nu/nu mice bearing established Ty82 BRD-NUT midline carcinoma xenografts.

  • Dosages

    ~100 mg/kg

  • Administration

    p.o.

Customer Product Validation

, , Mol Cancer Ther, 2016, 16(4 suppl 1):S263-S276

Data from [Data independently produced by , , Clin Cancer Res, 2018, 24(16):3941-3954]

Data from [Data independently produced by , , Clin Cancer Res, 2018, doi: 10.1158/1078-0432.CCR-18-1040]

Data from [Data independently produced by , , Sci Rep, 2016, 6:24100]

Selleck's Birabresib (OTX015) has been cited by 73 publications

Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
Targeting of mutant-p53 and MYC as a novel strategy to inhibit oncogenic SPAG5 activity in triple negative breast cancer [ Cell Death Dis, 2024, 15(8):603] PubMed: 39164278
RAPID resistance to BET inhibitors is mediated by FGFR1 in glioblastoma [ Sci Rep, 2024, 14(1):9284] PubMed: 38654040
HNF4α, SP1 and c-myc are master regulators of CNS autoimmunity [ J Autoimmun, 2023, 138:103053] PubMed: 37236124
"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction" [ J Exp Clin Cancer Res, 2023, 42(1):8] PubMed: 36604765
Combination drug screen targeting glioblastoma core vulnerabilities reveals pharmacological synergisms [ EBioMedicine, 2023, 95:104752] PubMed: 37572644
Combination drug screen targeting glioblastoma core vulnerabilities reveals pharmacological synergisms [ EBioMedicine, 2023, 95:104752] PubMed: 37572644
Pharmacological inhibition of bromodomain and extra-terminal proteins induces an NRF-2-mediated antiviral state that is subverted by SARS-CoV-2 infection [ PLoS Pathog, 2023, 19(9):e1011657] PubMed: 37747932
ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3-ITD [ Mol Oncol, 2023, 17(7):1402-1418] PubMed: 36567628
Epigenetic Regulation of MAP3K8 in EBV-Associated Gastric Carcinoma [ Int J Mol Sci, 2023, 24(3)1964] PubMed: 36768307

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.