2. MAPK/ERK Pathway
  3. MEK
  4. Refametinib

Refametinib  (Synonyms: BAY 869766; RDEA119)

Cat. No.: HY-14691 Purity: 99.82%
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Refametinib (BAY 869766; RDEA119) is an orally available, potent, non-ATP-competitive, selective, allosteric MEK1/MEK2 inhibitor with IC50s of 19 nM and 47 nM, respectively.

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

Refametinib Chemical Structure

Refametinib Chemical Structure

CAS No. : 923032-37-5

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10 mM * 1 mL in DMSO
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Customer Review

Based on 16 publication(s) in Google Scholar

Other Forms of Refametinib:

Refametinib Related Antibodies

Top Publications Citing Use of Products

    Refametinib purchased from MedChemExpress. Usage Cited in: Appl Sci. 2023 Mar 29, 13(7), 4340.

    Refametinib (50 nM; 1 h) significantly increases the expression of PARP and Caspase-3 in SCC4 Cells.

    Refametinib purchased from MedChemExpress. Usage Cited in: Appl Sci. 2023 Mar 29, 13(7), 4340.

    Refametinib (50 nM; 1 h) significantly decreases cell viability in SCC4 Cells.

    View All MEK Isoform Specific Products:

    View All Isoforms
    MEK1 MEK2 MEK5 MEK

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Refametinib (BAY 869766; RDEA119) is an orally available, potent, non-ATP-competitive, selective, allosteric MEK1/MEK2 inhibitor with IC50s of 19 nM and 47 nM, respectively.

    IC50 & Target[1]

    MEK1

    19 nM (IC50)

    MEK2

    47 nM (IC50)

    In Vitro

    Refametinib (BAY 869766; RDEA119) selectively binds directly to an allosteric pocket in the MEK1/2 enzymes. Refametinib potently inhibits MEK activity in enzyme inhibition assays in a non-ATP-competitive manner (MEK1 IC50=19 nM, MEK2 IC50=47 nM) determined through incorporation of radioactive phosphate from ATP into ERK as substrate. Refametinib potently inhibits MEK activity as measured by phosphorylation of ERK1/2 across several human cancer cell lines of different tissue origins and BRAF mutational status with EC50 values ranging from 2.5 to 15.8 nM. Refametinib inhibits anchorage-dependent growth of human cancer cell lines harboring the gain-of-function V600E BRAF mutant with GI50 values ranging from 67 to 89 nM. In contrast, Refametinib has significantly less growth-inhibitory potency against cell lines with wild-type BRAF (A431 cells) or MDA-MB-231 cells harboring a BRAF mutation G464V that shows minimal (<2-fold increase) enhancement of inherent kinase activity. Under anchorage-independent conditions, GI50 values for all cell lines tested are similar (40-84 nM). MDA-MB-231 and A431 cells are significantly more sensitive to Refametinib under anchorage-independent conditions[1].

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

    Refametinib Related Antibodies
    In Vivo

    Refametinib (BAY 869766; RDEA119) is an orally available, potent, non-ATP-competitive, highly selective inhibitor of MEK1/2, which is active in human tumor xenograft models and is well tolerated within the therapeutic exposure range in animals.The human melanoma A375 tumor xenograft is found to be sensitive to Refametinib treatment with 54% and 68% tumor growth inhibition (TGI) seen with 25 and 50 mg/kg/d administered orally on a once daily ×14 schedule. Significant tumor growth delay (TGD) and regressions are also observed in A375 tumors on this once-daily schedule. For example, five to eight complete or partial responses (CR/PR) and up to six tumor-free survivors (TFS) are observed. Administering Refametinib every other day at 100 mg/kg is less effective than daily dosing with either 25 or 50 mg/kg. When Refametinib is dosed on a twice-daily schedule, it is more effective than once-daily schedules[1].

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

    572.34

    Formula

    C19H20F3IN2O5S
    CAS No.
    Appearance

    Solid

    Color

    Light yellow to brown

    SMILES

    O=S(C1(C[C@H](O)CO)CC1)(NC(C(NC(C(F)=C2)=CC=C2I)=C3F)=C(OC)C=C3F)=O
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 31 mg/mL (54.16 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.7472 mL 8.7361 mL 17.4721 mL
    5 mM 0.3494 mL 1.7472 mL 3.4944 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

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

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

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    Volume (start)

    V1

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    Concentration (final)

    C2

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    Volume (final)

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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    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (4.37 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% Corn Oil

      Solubility: ≥ 2.5 mg/mL (4.37 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    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).
    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

    Purity: 99.82%

    SDS (252 KB)

    COA (253 KB) LCMS (453 KB)

    Handling Instructions (2659 KB)
    References
    Kinase Assay
    [1]

    MEK1 kinase activity is determined using mERK2 K52A T183A as the substrate. Recombinant MEK1 enzyme (5 nM) is first activated by 0.02 unit or 1.5 nM of RAF1 in the presence of 25 mM HEPES (pH 7.8), 1 mM MgCl2, 50 mM NaCl, 0.2 mM EDTA, and 50 μM ATP for 30 min at 25°C. The reactions are initiated by adding 2 μM of mERK2 K52A T183A and 2.5 μCi [γ-33P]ATP in a total volume of 20 μL. The MEK2 kinase activity is determined similarly except that activation by RAF1 is not needed and 11 nM of MEK2 enzyme (active) are used in the assays. Kinase profiling is performed. The Z'-LYTE biochemical assay is used. Refametinib is assayed in quadruplicate at 10 μM against 205 kinases[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Cell Assay
    [1]

    For anchorage-dependent growth inhibition experiments, A375, SK-Mel-28, A431, Colo205, HT-29, MDA-MB-231, and BxPC3 cell lines are plated in white 384-well plates at 1,000/20 μL/well or white 96-well microplates at 4,000/100 μL/well. After 24-h incubation at 37°C, 5% CO2, and 100% humidity, Refametinib is incubated for 48 h at 37°C and assayed using CellTiter-Glo. For the 96-well anchorage-independent growth assay, wells of an “ultralow binding” plate are filled with 60 μL of a 0.15% agarose solution in complete RPMI 1640. Then, 60 μL of complete RPMI 1640 containing 9,000 cells in 0.15% agarose are added per well. After 24 h, 60 μL of a 3× drug solution in agarose-free complete RPMI 1640 are added. After 7 d, 36 μL of 6× MTS reagent are added per well. After 2 h at 37°C, absorbance at 490 nm is determined on the M5 plate reader. Nonlinear curve fitting is performed using GraphPad Prism 4[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1]

    Mice[1]
    Female athymic nude mice are used for all the efficacy studies except for the Colo205 study 2, which used male mice. Mice are injected s.c. in the flank with 1×106 tumor cells (Colo205 and A431) or ~1 mm3 tumor fragments (A375 and HT-29). Tumor volumes are monitored by caliper measurements. For efficacy analysis, treatment is initiated when tumors are 80 to 185 mm3. Refametinib (25 and 50 mg/kg/d) is administered by oral gavage once daily or twice daily for 14 d or once every 2 d for 14 doses[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.7472 mL 8.7361 mL 17.4721 mL 43.6803 mL
    5 mM 0.3494 mL 1.7472 mL 3.4944 mL 8.7361 mL
    10 mM 0.1747 mL 0.8736 mL 1.7472 mL 4.3680 mL
    15 mM 0.1165 mL 0.5824 mL 1.1648 mL 2.9120 mL
    20 mM 0.0874 mL 0.4368 mL 0.8736 mL 2.1840 mL
    25 mM 0.0699 mL 0.3494 mL 0.6989 mL 1.7472 mL
    30 mM 0.0582 mL 0.2912 mL 0.5824 mL 1.4560 mL
    40 mM 0.0437 mL 0.2184 mL 0.4368 mL 1.0920 mL
    50 mM 0.0349 mL 0.1747 mL 0.3494 mL 0.8736 mL
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    Refametinib 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:

    Refametinib923032-37-5BAY 869766 RDEA119BAY869766BAY-869766RDEA119RDEA 119RDEA-119MEKMitogen-activated protein kinase kinaseMAPKKMAP2KallostericMEK1MEK2orallynon-ATP-competitivetumorInhibitorinhibitorinhibit

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