2. Epigenetics Stem Cell/Wnt MAPK/ERK Pathway
  3. Epigenetic Reader Domain ERK
  4. Molibresib besylate

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

Cat. No.: HY-13032B Purity: 97.04%
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Molibresib besylate (GSK 525762C; I-BET 762 besylate) is an orally active pan-BET inhibitor that targets and binds to BRD2, BRD3, BRD4 and BRDT. By competitively occupying acetylated lysine binding sites, Molibresib besylate disrupts the interaction between BET proteins and chromatin, thereby effectively inhibiting MYC expression and target gene transcription. Molibresib besylate exhibits broad antiproliferative activity, which not only inhibits cancer cell growth and induces growth arrest, but also downregulates mitosis-related genes and upregulates the level of p-ERK1/2. When combined with MEK inhibitors, Molibresib besylate shows a significant synergistic effect, reduces tumor burden in mouse models of leukemia, modulates the immune microenvironment and prolongs survival. Molibresib besylate is widely applicable to research related to acute myeloid leukemia, multiple myeloma, triple-negative breast cancer, small-cell lung cancer and various advanced refractory solid tumors.

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

CAS No. : 1895049-20-3

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Customer Review

Based on 21 publication(s) in Google Scholar

Other Forms of Molibresib besylate:

Molibresib besylate Related Antibodies

Top Publications Citing Use of Products

    Molibresib besylate purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Jul 2;15(1):5570.  [Abstract]

    HL-60 cells were treated daily with 25% GI50 concentrations of CM-444, CM-1758, Molibresib, and JQ1, or CM-444 or CM-1758 in combination with Molibresib or JQ1, for 48 hours. The cell differentiation experiment was performed by detecting CD11b by flow cytometry.

    Molibresib besylate purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Jul 2;15(1):5570.  [Abstract]

    ML-2 cells were treated daily with 25% GI50 concentrations of CM-444, CM-1758, Molibresib, and JQ1, or CM-444 or CM-1758 in combination with Molibresib or JQ1, for 48 hours. The cell differentiation experiment was performed by detecting CD11b by flow cytometry.

    Molibresib besylate purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Jul 2;15(1):5570.  [Abstract]

    q-PCR results of GATA2, PU.1, SCL and CEBPA in HL-60 cells after daily treatment with 25% GI50 concentrations of CM-444, CM-1758, Molibresib, JQ1, and CM-444 or CM-1758 in combination with Molibresib or JQ1 for 48 hours.

    Molibresib besylate purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Jul 2;15(1):5570.  [Abstract]

    q-PCR results of GATA2, PU.1, SCL and CEBPA in ML-2 cells after daily treatment with 25% GI50 concentrations of CM-444, CM-1758, Molibresib, JQ1, and CM-444 or CM-1758 in combination with Molibresib or JQ1 for 48 hours.

    Molibresib besylate purchased from MedChemExpress. Usage Cited in: Sci Adv. 2021 Feb 19;7(8):eabe4038.  [Abstract]

    Comparison of expression levels of molibresib targets BRD2, BRD3 and BRD4 between leukemic and nonleukemic cells of AML1.

    Molibresib besylate purchased from MedChemExpress. Usage Cited in: Nat Med. 2017 Sep;23(9):1055-1062.  [Abstract]

    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.

    Molibresib besylate purchased from MedChemExpress. Usage Cited in: Oncotarget. 2016 Jun 21;7(25):38319-38332.  [Abstract]

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

    View All ERK Isoform Specific Products:

    View All Isoforms
    ERK ERK1 ERK2 ERK5 ERK8

    • Biological Activity

    • Purity & Documentation

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    • Customer Review

    Description

    Molibresib besylate (GSK 525762C; I-BET 762 besylate) is an orally active pan-BET inhibitor that targets and binds to BRD2, BRD3, BRD4 and BRDT. By competitively occupying acetylated lysine binding sites, Molibresib besylate disrupts the interaction between BET proteins and chromatin, thereby effectively inhibiting MYC expression and target gene transcription. Molibresib besylate exhibits broad antiproliferative activity, which not only inhibits cancer cell growth and induces growth arrest, but also downregulates mitosis-related genes and upregulates the level of p-ERK1/2. When combined with MEK inhibitors, Molibresib besylate shows a significant synergistic effect, reduces tumor burden in mouse models of leukemia, modulates the immune microenvironment and prolongs survival. Molibresib besylate is widely applicable to research related to acute myeloid leukemia, multiple myeloma, triple-negative breast cancer, small-cell lung cancer and various advanced refractory solid tumors[1][2][3].

    IC50 & Target

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

    Molibresib (besylate) (10-500 nM; 7 days, single agent; 0.05-1.5 μM; 7 days, in combination with trametinib) alone inhibits primary NrasG12D/+;Asxl1-/- AML cell proliferation in vitro, and in combination with trametinib exerts synergistic anti-proliferative effects on these cells[1].
    Molibresib (besylate) (500 nM; 24-96 h) down-regulates MYC signatures and transiently down-regulates mitotic genes in RKO colorectal cancer cells, and combined treatment with trametinib results in sustained, robust down-regulation of mitotic, E2F, and apoptotic signatures that is greater than either single agent[2].
    Molibresib (besylate) (500 nM; 1-6 days) induces transient G1 arrest in RKO colorectal cancer cells and modest G1 arrest in BxPC-3 pancreatic cancer cells, and combined treatment with trametinib results in sustained G1 arrest in RKO cells and cell death in BxPC-3 cells[2].
    Molibresib (besylate) (100 nM to 1 μM; 1-6 days) up-regulates p-ERK1/2 levels in RPMI-8226 multiple myeloma, NCI-H510 small cell lung carcinoma, and NCI-H526 small cell lung carcinoma cells, and this up-regulation is reversed by co-treatment with MEK inhibitors[2].
    Molibresib (besylate) (500 nM (RPMI-8226), 1 μM (NCI-H510); 96 h) up-regulates ERK activation-associated genes in RPMI-8226 multiple myeloma and NCI-H510 small cell lung carcinoma cells, and this up-regulation is reversed by co-treatment with MEK inhibitors[2].

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

    Molibresib besylate Related Antibodies

    Cell Cycle Analysis[2]

    Cell Line: RKO (BRAFmut, NF1mut CRC) cells, BxPC-3 (KRASmut pancreatic cancer) cells
    Concentration: 500 nM
    Incubation Time: 1 day (cell cycle analysis); 6 days (cell cycle analysis)
    Result: Induced substantial G1 arrest in RKO cells at 1 day, which diminished by 6 days.
    Induced modest G1 arrest in BxPC-3 cells at 6 days.
    Resulted in sustained G1 arrest in RKO cells (with a greater proportion of cells in G1 at 6 days than at 1 day) when combined with trametinib.
    Caused substantial sub-G1 accumulation (indicative of cell death) in BxPC-3 cells at 6 days when combined with trametinib.

    Western Blot Analysis[2]

    Cell Line: RPMI-8226 (KRASmut MM) cells, NCI-H510 (NF1mut SCLC) cells, NCI-H526 (SCLC) cells
    Concentration: 250 nM, 500 nM, 1 μM (RPMI-8226); 100 nM, 1 μM (NCI-H510); 500 nM, 100 nM, 1 μM (NCI-H526)
    Incubation Time: 4 days (RPMI-8226); 3 days (NCI-H510); 1 day, 6 days, 3 days (NCI-H526)
    Result: Increased p-ERK1/2 levels in RPMI-8226 cells after 4 days of single-agent treatment.
    Increased p-ERK1/2 levels in NCI-H510 cells after 3 days of single-agent treatment.
    Increased p-ERK1/2 levels in NCI-H526 cells after 1 and 6 days of single-agent treatment.
    Reversed the Molibresib (besylate)-induced up-regulation of p-ERK1/2 when co-treated with MEK inhibitors (trametinib in RPMI-8226; PD0325901 in NCI-H510 and NCI-H526).

    Real Time qPCR[2]

    Cell Line: RPMI-8226 (KRASmut MM) cells, NCI-H510 (NF1mut SCLC) cells
    Concentration: 500 nM (RPMI-8226); 1 μM (NCI-H510)
    Incubation Time: 96 h
    Result: Up-regulated ERK activation-associated genes (DUSP4, DUSP6, SPRED1, SPRED2, EGR1, ETV5, SPRY4, SPRY2) in RPMI-8226 cells with single-agent treatment.
    Up-regulated ERK activation-associated genes (DUSP4, DUSP6, SPRED1, SPRED2, EGR1, ETV5, SPRY4, SPRY2) in NCI-H510 cells with single-agent treatment.
    Down-regulated ERK activation-associated genes compared to Molibresib (besylate) monotherapy when co-treated with MEK inhibitors (trametinib in RPMI-8226; PD0325901 in NCI-H510).
    In Vivo

    Combination of Molibresib besylate and Trametinib (HY-10999) reduces leukemia burden, reverses the immunosuppressive microenvironment, enhances the cytotoxicity of CD8+ T cells, and significantly prolongs survival in a mouse model of NrasG12D/+;Asxl1-/- acute myeloid leukemia[1].
    Combination therapy with Molibresib besylate and Trametinib significantly prolongs survival in a human CMML xenograft mouse model harboring concurrent RAS and ASXL1 mutations[1].
    Combination treatment with Molibresib besylate (15 mg/kg; p.o.; once daily) and Trametinib (1 mg/kg; p.o.; once daily) delays tumor growth in female NCr nu/nu mice inoculated with RKO colorectal cancer xenografts and MDA-MB-231 triple-negative breast cancer xenografts, respectively, and the combined effect is stronger than that of Molibresib besylate alone[2].
    Combination treatment with Molibresib besylate (25 mg/kg; p.o.; once daily) and Trametinib (1 mg/kg; p.o.; once daily) delays tumor growth in female CB.17 SCID mice inoculated with RPMI-8226 multiple myeloma xenografts, and the combined effect is stronger than that of Molibresib besylate alone[2].

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

    Animal Model: NCr nu/nu mice with Colorectal cancer (female, 10 or 11 weeks old, implanted with RKO cells for xenograft modeling)[2]
    Dosage: 15 mg/kg (in combination with trametinib 1 mg/kg)
    Administration: p.o.; once daily
    Result: Produced significantly greater tumor growth delay, with statistically significant difference in time to tumor endpoint.
    Animal Model: NCr nu/nu mice with Triple-negative breast cancer (female, 10 or 11 weeks old, implanted with MDA-MB-231 cells for xenograft modeling)[2]
    Dosage: 15 mg/kg (in combination with trametinib 1 mg/kg)
    Administration: p.o.; once daily
    Result: Produced significantly greater tumor growth delay, with statistically significant difference in time to tumor endpoint.
    Animal Model: CB.17 SCID mice with Multiple myeloma (female, 12 weeks old, implanted with RPMI-8226 cells for xenograft modeling)[2]
    Dosage: 25 mg/kg (in combination with trametinib 0.1 mg/kg)
    Administration: p.o.; once daily
    Result: Produced significantly greater tumor growth delay, with statistically significant difference in time to tumor endpoint.
    Molecular Weight

    582.07

    Formula

    C28H28ClN5O5S
    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    ClC1=CC=C(C2=N[C@@H](CC(NCC)=O)C3=NN=C(C)N3C4=CC=C(OC)C=C24)C=C1.O=S(C5=CC=CC=C5)(O)=O
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage

    4°C, sealed storage, away from moisture

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    Solvent & Solubility
    In Vitro: 

    DMSO : 25 mg/mL (42.95 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.7180 mL 8.5900 mL 17.1801 mL
    5 mM 0.3436 mL 1.7180 mL 3.4360 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

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

      Solubility: ≥ 2.67 mg/mL (4.59 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.67 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (26.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.67 mg/mL (4.59 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.67 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (26.7 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

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    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation
    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.7180 mL 8.5900 mL 17.1801 mL 42.9502 mL
    5 mM 0.3436 mL 1.7180 mL 3.4360 mL 8.5900 mL
    10 mM 0.1718 mL 0.8590 mL 1.7180 mL 4.2950 mL
    15 mM 0.1145 mL 0.5727 mL 1.1453 mL 2.8633 mL
    20 mM 0.0859 mL 0.4295 mL 0.8590 mL 2.1475 mL
    25 mM 0.0687 mL 0.3436 mL 0.6872 mL 1.7180 mL
    30 mM 0.0573 mL 0.2863 mL 0.5727 mL 1.4317 mL
    40 mM 0.0430 mL 0.2148 mL 0.4295 mL 1.0738 mL
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    Molibresib besylate Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    Molibresib besylate1895049-20-3GSK 525762C I-BET 762 besylateEpigenetic Reader DomainERKExtracellular signal regulated kinaseschronic myelomonocytic leukemiaBRDTBRD3BRD4colorectal cancerBRD2MYCtriple-negative breast canceracetylated histonesacute myeloid leukemiaInhibitorinhibitorinhibit

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