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  2. Epigenetic Reader Domain
  3. Molibresib

Molibresib (Synonyms: GSK 525762A; I-BET 762)

Cat. No.: HY-13032 Purity: 99.85%
Handling Instructions

Molibresib (GSK 525762A; I-BET 762) is a BET bromodomain inhibitor with IC50 of 32.5-42.5 nM.

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

Molibresib Chemical Structure

Molibresib Chemical Structure

CAS No. : 1260907-17-2

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100 mg USD 750 In-stock
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Customer Review

Based on 12 publication(s) in Google Scholar

Other Forms of Molibresib:

Top Publications Citing Use of Products

    Molibresib purchased from MCE. Usage Cited in: Oncotarget. 2016 Jun 21;7(25):38319-38332.

    iBET762 partially disrupts the interaction between full-length ERG and BRD4 (A), and between T1-E4 ERG and BRD4 (B).

    Molibresib purchased from MCE. Usage Cited in: Nat Med. 2017 Sep;23(9):1055-1062.

    Western blot of WCL of C4-2 cells treated with vehicle (DMSO) or different doses of JQ1 or i-BET for 24 h. Actin is used as a loading control.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Molibresib (GSK 525762A; I-BET 762) is a BET bromodomain inhibitor with IC50 of 32.5-42.5 nM.

    IC50 & Target

    IC50: 32.5-42.5 nM (BET)[1]

    In Vitro

    Molibresib (I-BET 762) shows the highest affinity interaction with BET. Molibresib binds to the tandem bromodomains of BET with high affinity (dissociation constant Kd of 50.5-61.3 nM). Molibresib displaces, with high efficacy (half-maximum inhibitory concentration IC50 of 32.5-42.5 nM), a tetra-acetylated H4 peptide that had been pre-bound to tandem bromodomains of BET[1]. Molibresib has high affinity for BD1/BD2 domain of BRD2/3/4 proteins. Molibresib treatment leads to a reduction in the recruitment of all three proteins to chromatin[2]. Molibresib inhibits OPM-2 cell proliferation with IC50 of 60.15 nM[3].

    In Vivo

    The antimyeloma activity of Molibresib (I-BET 762) is tested dosed orally in an in vivo systemic xenograft model generated by injecting OPM-2 cells into NOD-SCID mice. Daily oral doses of Molibresib up to 10 mg/kg and 30 mg/kg given every other day are well tolerated with no clear impact on body weight compared with vehicle control. The plasma hLC concentration is significantly reduced in mice treated with Molibresib[3].

    Clinical Trial
    Molecular Weight

    423.90

    Formula

    C₂₂H₂₂ClN₅O₂

    CAS No.

    1260907-17-2

    SMILES

    ClC1=CC=C(C2=N[[email protected]@H](CC(NCC)=O)C3=NN=C(C)N3C4=CC=C(OC)C=C24)C=C1

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 33.33 mg/mL (78.63 mM; Need ultrasonic)

    H2O : < 0.1 mg/mL (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.3590 mL 11.7952 mL 23.5905 mL
    5 mM 0.4718 mL 2.3590 mL 4.7181 mL
    10 mM 0.2359 mL 1.1795 mL 2.3590 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

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

      Solubility: ≥ 2.5 mg/mL (5.90 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [2]

    VCaP, LNCaP, 22RV1, DU145 and PC3 prostate cancer cell lines are seeded in 96-well plates at 2000-10,000 cells/well (optimum density for growth) in a total volume of 100μL media containing 10% FBS. Serially diluted compounds in 100μL media are added to the cells 12hr later. Following 96 hr. incubation, cell viability is assessed by Cell-Titer GLO. The values are normalized and IC50 is calculated using GraphPad Prism software. For long-term colony formation assay, 10,000-50,000 cells/well are seeded in six-well plates and treated with either 100 nM or 500 nM of JQ1 or DMSO. After 12 days cells are fixed with methanol, stained with crystal violet and photographed. For colorimetric assays, the stained wells are treated with 500μL 10% acetic acid and the absorbance is measured at 560nm using a spectrophotometer[2].

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

    Animal Administration
    [3]

    Mice[3]
    The antimyeloma efficacy of orally administered Molibresib is tested in a systemic xenograft myeloma model. For this purpose, sublethally irradiated (200 cGy) NOD/SCID mice age 9 to 11 weeks are given 107 OPM-2 myeloma cells via tail vein injection. On day 15 following inoculation, animals are started on oral treatment with Molibresib at escalating doses or vehicle (1% methylcellulose and 0.2% sodium lauryl sulfate), which is continued up to day 83. Specifically, 1 group of mice are treated with vehicle and 4 groups with different dosing schedules of Molibresib: 3 mg/kg per day; 10 mg/kg per day; 30 mg/kg on alternate days; and 30 to 20 mg/kg per day (ie, 30 mg/kg per day for 14 days, followed by 2 weeks [days 15 to 31] off treatment [drug is withheld due to a decline in body weight until animals has regained weight], follow by 20 mg/kg per day until termination of the experiment [days 43 to 82]). Blood samples (~70 μL) are removed at 0.5 hours after oral administration of Molibresib on day 15 (treatment initiation); days 27, 45, and 82 (3, 10, and 20 to 30 mg/kg once per day groups only); and day 83 (30 mg/kg once every other day group only). The blood is centrifuged to obtain 20 μL plasma and stored at -20°C prior to analysis for Molibresib by using a specific liquid chromatography/mass spectrometry/mass spectrometry assay.

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

    References

    Purity: 99.85%

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    Keywords:

    MolibresibGSK 525762AI-BET 762Epigenetic Reader DomainInhibitorinhibitorinhibit

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    Cat. No.:
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