1. Epigenetics
  2. Epigenetic Reader Domain

OTX-015 (Synonyms: MK-8628; Birabresib)

Cat. No.: HY-15743 Purity: 99.75%
Handling Instructions

OTX-015 is a new potent BRD2/3/4 inhibitor for cell adhesion with IC50 values from 92 to 112 nM.

For research use only. We do not sell to patients.

OTX-015 Chemical Structure

OTX-015 Chemical Structure

CAS No. : 202590-98-5

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 92 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
5 mg USD 84 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 108 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 300 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
100 mg USD 504 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
200 mg USD 960 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
500 mg   Get quote  
1 g   Get quote  

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Customer Review

    OTX-015 purchased from MCE. Usage Cited in: EMBO Mol Med. 2018 Apr 12. pii: e8446.

    NRAS-mutant melanoma cells grown as collagen-embedded 3D spheroids are treated with DMSO, 0.1 μM MEKi PD901, 0.5 μM BETi (JQ-1 or OTX-015), or BETi+MEKi combination for 5 days. Spheroids are stained with Calcein (AM) (green; live cells) and EtBr (red; dead cells) and imaged using a fluorescence microscope.

    OTX-015 purchased from MCE. Usage Cited in: Cancer Res. 2018 Aug 16. pii: canres.1327.2018.

    WT and S47 E1A/RAS cells are treated with 10μM CDDP for 24 hours in the presence or absence of the protein synthesis inhibitor Cycloheximide (2.5 g/mL). Cell lysates are subjected to Western blot analysis, and immunoblotted for cleaved caspase-3, p53, p21, and HSP90 (loading control). CDDP: cisplatin

    OTX-015 purchased from MCE. Usage Cited in: Cancer Res. 2018 Aug 16. pii: canres.1327.2018.

    WT and S47 E1A/RAS cells are treated with 10 M Cisplatin (CDDP) for 24 hours. Cells are then fractionated into three fractions: whole cell lysate (W), mitochondria (M), and cytosol (C).
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    OTX-015 is a new potent BRD2/3/4 inhibitor for cell adhesion with IC50 values from 92 to 112 nM.

    IC50 & Target

    IC50: 92-112 nM (BRD2, BRD3, BRD4)[1]

    In Vitro

    OTX015 (500 nM) exposure induces a strong decrease of BRD2, BRD4 and c-MYC and increase of HEXIM1 proteins, while BRD3 expression is unchanged. c-MYC, BRD2, BRD3, BRD4 and HEXIM1 mRNA levels do correlate however with viability following exposure to OTX015. Sequential combinations of OTX015 with other epigenetic modifying drugs, panobinostat and azacitidine have a synergic effect on growth of the KASUMI cell line[2]. OTX015 (0.1, 1, 5 μM) treatment induces HIV-1 full-length transcripts and viral outgrowth in resting CD4+ T cells from infected individuals receiving suppressive antiretroviral therapy (ART), while exerting minimal toxicity and effects on T cell activation. OTX015-mediated activation of HIV-1 involves an increase in CDK9 occupancy and RNAP II C-terminal domain (CTD) phosphorylation[3].

    In Vivo

    In MDA-MB-231 murine xenografts, tumor mass is significantly (p < 0.05) reduced by OTX015 (50 mg/kg) with respect to vehicle-treated animals. OTX015 in combination with 2 mg/kg everolimus shows more effective activity than OTX015 alone[4].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 49 mg/mL (99.60 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.0326 mL 10.1628 mL 20.3256 mL
    5 mM 0.4065 mL 2.0326 mL 4.0651 mL
    10 mM 0.2033 mL 1.0163 mL 2.0326 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (5.08 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (5.08 mM); Clear solution

    References
    Kinase Assay
    [3]

    TZMbl cells, grown in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% FBS, are plated at 1×105 cells/well in 24-well culture plates 24 h before transfection and then transfected with Tat or pcDNA 3.1 plasmid using Lipofectamine 2000. Primary CD4+ T cells (5 × 106) isolated from healthy donors are transfected with Tat or pcDNA 3.1 plasmid at the presence of LTR-Luc construct and then plated in 6-well culture plates. At 24 h post-transfection, the cells are mock-treated or treated with OTX015. At 48 h post-treatment, cells are lysed and luciferase activity is measured using the Dual-Luciferase Reporter Assay Kit.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    For the MTT assay, cells are seeded in 24-well plates at 1×106 per well and treated with OTX015 (0.01 nM-10 μM) for 72 h. Cells are transferred to 96-well plates and incubated with 0.5 mg/mL 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) in the dark at 37°C for 4 h. Cells are then lysed with 25% sodium dodecyl sulfate (SDS) lysis buffer and absorbance is read at 570 nm using a Microplate Reader. Three independent experiments are run for each cell line and untreated cells are used as negative controls.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [4]

    Mice are subcutaneously injected in the right flank with 10×106 MDA-MB-231 cells. When average tumor weight is appr 130 mg, mice are randomized (nine animals/group) to one of the following experimental groups: vehicle (for OTX15, water, twice daily, oral; for everolimus vehicle, 5% Tween-80/5% polyethylene glycol 400, thrice weekly, intraperitoneal); 50 mg/kg OTX015, twice daily, oral; 2 mg/kg everolimus, thrice weekly, intraperitoneal; 50 mg/kg OTX015 + 2 mg/kg everolimus, according to the single agent dosing schedules. In the experiment with paclitaxel, mice are randomized (eight animals/group) to vehicle (cremophor:ethanol 1:1, then diluted 1:5 with saline; once weekly, intravenous) or 0.15 mg/kg paclitaxel, once weekly, intravenous. Mice are sacrified at the first sign of severe distress and tumors are collected. Tumor weight (1 mm3 = 1 mg) is determined using the formula d2 × D/2, where 'd' and 'D' are the minor and major diameters of the tumor in mm, respectively. Growth curves of each tumor are normalized with respect to volume at the start of treatment. The doubling time (Td) of each untreated tumor is calculated by exponential fit of the whole growth curve. Treatment efficacy is evaluated based on T/C%, absolute growth delay (AGD) and log cell kill (LCK) parameters. In T/C%, T and C are the mean tumor weight of treated and control groups, respectively.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    491.99

    Formula

    C₂₅H₂₂ClN₅O₂S

    CAS No.

    202590-98-5

    SMILES

    O=C(NC1=CC=C(O)C=C1)C[[email protected]]2C3=NN=C(C)N3C4=C(C(C)=C(C)S4)C(C5=CC=C(Cl)C=C5)=N2

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.75%

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    Product Name:
    OTX-015
    Cat. No.:
    HY-15743
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    Cat. No.: HY-15743