1. MAPK/ERK Pathway Autophagy Apoptosis
  2. MEK Autophagy Apoptosis
  3. Mirdametinib

Mirdametinib  (Synonyms: PD0325901; PD325901)

Cat. No.: HY-10254 Purity: 99.95%
SDS COA Handling Instructions

PD0325901 (PD325901) est un inhibiteur de MEK qui est oralement actif, sélectif et non-ATP-compétitif avec un IC50 de 0,33 nM. PD0325901 présente un Kiapp de 1 nM contre les MEK1 et MEK2 activés. PD0325901 supprime l'expression de p-ERK1/2 et induit l'apoptose. PD0325901 a une activité anticancéreuse pour un large éventail de xénogreffes de tumeurs humaines.

Mirdametinib (PD0325901) is an orally active, selective and non-ATP-competitive MEK inhibitor with an IC50 of 0.33 nM. Mirdametinib exhibits a Kiapp of 1 nM against activated MEK1 and MEK2. Mirdametinib suppresses the expression of p-ERK1/2 and induces apoptosis. Mirdametinib has anti-cancer activity for a broad spectrum of human tumor xenografts.

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

Mirdametinib Chemical Structure

Mirdametinib Chemical Structure

CAS No. : 391210-10-9

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Customer Review

Based on 99 publication(s) in Google Scholar

Other Forms of Mirdametinib:

Top Publications Citing Use of Products

95 Publications Citing Use of MCE Mirdametinib

WB

    Mirdametinib purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2020 Apr 2;524(2):280-287.  [Abstract]

    Western blot analysis of Tcf7l1 protein levels in mESCs pre-treated with D4476 or DMAT and then treated with CHIR or PD03 for 24 h.

    Mirdametinib purchased from MedChemExpress. Usage Cited in: J Exp Clin Cancer Res. 2018 Jun 28;37(1):128.  [Abstract]

    MHCC-97H cells are transfected with control or supervillin-specific siRNA for 48 h, exposed to hypoxia for 16 h, and lysates are assayed for the relative amounts of GTP-loaded (activated) Rac1, Cdc42, and RhoA. Cells that have been transfected with control RNAi are treated with a PD0325901 or SB239063 before assaying for GTP-Rac1, Cdc42, and RhoA levels.

    Mirdametinib purchased from MedChemExpress. Usage Cited in: Viruses. 2018 Apr 13;10(4). pii: E191.  [Abstract]

    H2.35 cells are serum starved for 72 h and then were pre-treated with either DMSO or BI-D1870 (p90 IN, 10 µM). Cells are infected with MP12 (MOI 5) for one hour, followed by removal of viral inoculum, and addition of growth medium containing DMSO or p90 IN (10 µM). At 18 hpi, cell lysates are collected for western blot analysis.

    Mirdametinib purchased from MedChemExpress. Usage Cited in: Viruses. 2018 Apr 13;10(4). pii: E191.  [Abstract]

    H2.35 cells are serum starved for 72 h and then are pre-treated with either DMSO or 10 µM PD0325901 (ERK IN). Cells are infected with MP12 (MOI 5) for one hour, followed by removal of viral inoculum, and addition of growth medium containing DMSO or 10 µM ERK IN. At 18 hpi, cell lysates are collected for western blot analysis.

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    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Mirdametinib (PD0325901) is an orally active, selective and non-ATP-competitive MEK inhibitor with an IC50 of 0.33 nM. Mirdametinib exhibits a Kiapp of 1 nM against activated MEK1 and MEK2. Mirdametinib suppresses the expression of p-ERK1/2 and induces apoptosis. Mirdametinib has anti-cancer activity for a broad spectrum of human tumor xenografts[1][2][3].

    IC50 & Target[1][2]

    MEK1

    1 nM (Ki)

    MEK2

    1 nM (Ki)

    MEK

    0.33 nM (IC50)

    Cellular Effect
    Cell Line Type Value Description References
    A-375 IC50
    13 nM
    Compound: PD325901
    Antiproliferative activity against human A375 cells expressing BRAF V600E mutant after 72 hrs by Cell titer-glo assay
    Antiproliferative activity against human A375 cells expressing BRAF V600E mutant after 72 hrs by Cell titer-glo assay
    [PMID: 23474388]
    A-431 IC50
    < 0.014 μM
    Compound: PD-0325901
    Inhibition of MEK/ERK signaling pathway in TNFalpha-stimulated human A431 cells transfected with COT siRNA assessed as reduction in ERK1/2 phosphorylation incubated for 60 mins followed by stimulation with TNFalpha for 10 mins by Western blot analysis
    Inhibition of MEK/ERK signaling pathway in TNFalpha-stimulated human A431 cells transfected with COT siRNA assessed as reduction in ERK1/2 phosphorylation incubated for 60 mins followed by stimulation with TNFalpha for 10 mins by Western blot analysis
    [PMID: 27502541]
    A-431 IC50
    0.038 μM
    Compound: PD-0325901
    Inhibition of MEK/ERK signaling pathway in EGF-stimulated human A431 cells transfected with COT siRNA assessed as reduction in ERK1/2 phosphorylation incubated for 60 mins followed by stimulation with EGF for 10 mins by Western blot analysis
    Inhibition of MEK/ERK signaling pathway in EGF-stimulated human A431 cells transfected with COT siRNA assessed as reduction in ERK1/2 phosphorylation incubated for 60 mins followed by stimulation with EGF for 10 mins by Western blot analysis
    [PMID: 27502541]
    A549 IC50
    0.06 μM
    Compound: PD0325901
    Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay
    Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay
    [PMID: 32305784]
    COLO 205 GI50
    0.2 nM
    Compound: 4; PD0325901
    Antiproliferative activity against human COLO205 cells assessed as reduction in cell growth after 3 days by WST8 assay
    Antiproliferative activity against human COLO205 cells assessed as reduction in cell growth after 3 days by WST8 assay
    [PMID: 31730343]
    HCT-116 IC50
    0.09 μM
    Compound: PD0325901
    Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay
    Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay
    [PMID: 32305784]
    HL-60 IC50
    0.0013 μM
    Compound: PD0325901
    Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay
    Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay
    [PMID: 32305784]
    HT-29 GI50
    3.1 nM
    Compound: 4; PD0325901
    Antiproliferative activity against human HT-29 cells assessed as reduction in cell growth after 3 days by MTT assay
    Antiproliferative activity against human HT-29 cells assessed as reduction in cell growth after 3 days by MTT assay
    [PMID: 31730343]
    MDA-MB-231 IC50
    0.082 μM
    Compound: PD0325901
    Antiproliferative activity against human MDA-MB-231 cells harboring KRAS G13D/BRAF G464V mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay
    Antiproliferative activity against human MDA-MB-231 cells harboring KRAS G13D/BRAF G464V mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay
    [PMID: 32305784]
    MDA-MB-231 GI50
    1 μM
    Compound: PD-0325901
    Antiproliferative activity against human MDA-MB-231 cells incubated for 72 hrs by CellTiter-Glo luminescence assay
    Antiproliferative activity against human MDA-MB-231 cells incubated for 72 hrs by CellTiter-Glo luminescence assay
    [PMID: 30802730]
    Sf21 IC50
    > 25 μM
    Compound: PD-0325901
    Inhibition of human COT (66 to 395 residues) expressed in Sf21 cells using 5-Fluo-Ahx-AGAGSGQLIDSNleANSFVGTR-NH2 as substrate after 60 mins by caliper microfluidic mobility shift assay
    Inhibition of human COT (66 to 395 residues) expressed in Sf21 cells using 5-Fluo-Ahx-AGAGSGQLIDSNleANSFVGTR-NH2 as substrate after 60 mins by caliper microfluidic mobility shift assay
    [PMID: 27502541]
    SK-MEL-28 GI50
    2.9 nM
    Compound: 4; PD0325901
    Antiproliferative activity against human SK-MEL-28 cells assessed as reduction in cell growth after 3 days by MTT assay
    Antiproliferative activity against human SK-MEL-28 cells assessed as reduction in cell growth after 3 days by MTT assay
    [PMID: 31730343]
    SU-DHL-1 GI50
    350 nM
    Compound: 1; PD0325901
    Antiproliferative activity against human SU-DHL-1 cells incubated for 3 days by WST8 assay
    Antiproliferative activity against human SU-DHL-1 cells incubated for 3 days by WST8 assay
    [PMID: 33284613]
    UACC-257 GI50
    0.2 nM
    Compound: 4; PD0325901
    Antiproliferative activity against human UACC257 cells assessed as reduction in cell growth after 3 days by MTT assay
    Antiproliferative activity against human UACC257 cells assessed as reduction in cell growth after 3 days by MTT assay
    [PMID: 31730343]
    In Vitro

    Mirdametinib (PD325901; 0.0064, 0.032, 0.16, 0.8, 4, 20, 100 nM; for 2 days) inhibits the growth of Papillary thyroid carcinomas (PTC) cell lines (TPC-1 cells and K2 cells) with GC50 of 11 nM and 6.3 nM, respectively[3].
    Mirdametinib (100 nmol/L; for 4 days) induces apoptosis in K2 cells (top) or TPC-1 cells[3].
    Mirdametinib (0.1, 1, 10, 100, 1000 nM; for 1 hour) suppresses the expression of p-ERK1/2 in K2 cells (top) or TPC-1 cells[3].
    Mirdametinib prevents the growth of melanoma cell lines. Mirdametinib significantly prevents the the growth of PTC cells harboring a BRAF mutation at very low concentration (10 nM)[3].

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

    In Vivo

    Mirdametinib (25 mg/kg, p.o.) inhibits phosphorylation of ERK by more than 50% at 24 hours post-dosing. Mirdametinib (25 mg/kg/day; po) produces a 70% incidence of complete tumor responses (C26 model)[2].
    Mirdametinib (20-25 mg/kg/day; oral gavage; for 3 weeks (5 consecutive days/week)) suppresses tumor growth completely in mice inoculated with PTC cells carrying a BRAF mutation (K2) and significantly decreased tumor growth in mice inoculated with PTC cells carrying the RET/PTC1 rearrangement (TPC-1) in athymic Ncr-nu/nu mice at ages 6 to 8 weeks[3].

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

    Clinical Trial
    Molecular Weight

    482.19

    Formula

    C16H14F3IN2O4

    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    O=C(C1=CC=C(C(F)=C1NC2=CC=C(I)C=C2F)F)NOC[C@H](O)CO

    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 : ≥ 56 mg/mL (116.14 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 2.0739 mL 10.3694 mL 20.7387 mL
    5 mM 0.4148 mL 2.0739 mL 4.1477 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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    • 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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    C2

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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: ≥ 2.08 mg/mL (4.31 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: ≥ 2.08 mg/mL (4.31 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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:

    Dosage

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    (per animal)

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    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 +
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    %
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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).
    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: 99.95%

    References
    Kinase Assay
    [1]

    Incorporation of 32P into myelin basic protein (MBP) is assayed in the presence of a glutathione S-transferase fusion protein containing p44MAP kinase (GST-MAPK) and a glutathione S-transferase protein containing p45MEK (GST-MEK). The assay solution contained 20 mM HEPES, pH 7.4, 10 mM MgCl2, 1 mM MnCl2, 1 mM EGTA, 50 mM [gamma-32P]ATP, 10 mg GST-MEK, 0.5 mg GST-MAPK and 40 mg MBP in a final volume of 100 mL. Reactions are stopped after 20 minutes by addition of trichloroacetic acid and filtered through a GF/C filter mat. 32P retained on the filter mat is determined using a 1205 Betaplate. PD0325901 is assessed at various dose ranges in order to determine dose response curves.

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

    Cell Assay
    [2]

    PTC cells (1×104) are seeded in 24-well plates with 1 mL of medium for 4 days in a 37°C incubator. MEK inhibitor PD0325901 at varying concentrations is added to the cells in triplicate on day 0. MTT dissolved in 0.8% NaCl solution at 5 mg/mL is added to each well (0.2 mL) on day 2 to test GC50 or every day for cell growth curves. The cells are incubated at 37°C for 3 hours with MTT. The liquid is then aspirated from the wells and discarded. Stained cells are dissolved in 0.5 mL of DMSO and their absorption at 570 nm is measured using a Synergy HT multidetection microplate reader. For GC50, cell growth is calculated as 100×(T−T0)/(C−T0), where T is the optical density of the wells treated with inhibitors after a 48-hour period, T0 is the optical density at time zero, and C is the control optical density with DMSO only.

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

    Animal Administration
    [2]

    Mice (10-14 per group) are anesthetized s.c. with a cocktail. K2 and TPC-1 cells stably infected with a retrovirus expressing luciferase (5×105 cells in 5 μL RPMI1640 medium) are inoculated into the thyroid gland, and the mice are monitored weekly for tumor growth by Xenogen using Living Image 3.0 software. One week after inoculation, PD0325901 is dissolved in 80 mM citric buffer (pH 7) by sonication and given to mice daily by oral gavage (20-25 mg/kg) for 3 weeks (5 consecutive days/week). Mice are sacrificed only due to tumor burden or loss of 20% of body weight. Tumor sizes are measured with calipers and tumor volume (V) is calculated by the formula (V=length×width×depth). Control mice are given 80 mM citric buffer (pH 7) alone. All in vivo experiments are done at least twice.

    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, 6 months; -20°C, 1 month. 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 2.0739 mL 10.3694 mL 20.7387 mL 51.8468 mL
    5 mM 0.4148 mL 2.0739 mL 4.1477 mL 10.3694 mL
    10 mM 0.2074 mL 1.0369 mL 2.0739 mL 5.1847 mL
    15 mM 0.1383 mL 0.6913 mL 1.3826 mL 3.4565 mL
    20 mM 0.1037 mL 0.5185 mL 1.0369 mL 2.5923 mL
    25 mM 0.0830 mL 0.4148 mL 0.8295 mL 2.0739 mL
    30 mM 0.0691 mL 0.3456 mL 0.6913 mL 1.7282 mL
    40 mM 0.0518 mL 0.2592 mL 0.5185 mL 1.2962 mL
    50 mM 0.0415 mL 0.2074 mL 0.4148 mL 1.0369 mL
    60 mM 0.0346 mL 0.1728 mL 0.3456 mL 0.8641 mL
    80 mM 0.0259 mL 0.1296 mL 0.2592 mL 0.6481 mL
    100 mM 0.0207 mL 0.1037 mL 0.2074 mL 0.5185 mL
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      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.

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