2. Others Metabolic Enzyme/Protease Cell Cycle/DNA Damage
  3. Oxidative Phosphorylation Mitochondrial Metabolism DNA/RNA Synthesis
  4. IMT1

IMT1 is a first-in-class specific and noncompetitive human mitochondrial RNA polymerase (POLRMT) inhibitor. IMT1 causes a conformational change of POLRMT, which blocks substrate binding and transcription in a dose-dependent way in vitro. IMT1 reduces deoxynucleoside triphosphate levels and citric acid cycle intermediates, resulting in a marked depletion of cellular amino acid levels. IMT1 has the potential for mitochondrial transcription disorders related diseases.

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IMT1 Chemical Structure

IMT1 Chemical Structure

CAS No. : 2304621-31-4

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Solid + Solvent
10 mM * 1 mL in DMSO
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Customer Review

Based on 4 publication(s) in Google Scholar

IMT1 Related Antibodies

Top Publications Citing Use of Products

    IMT1 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2023 Feb 16;14(1):872.  [Abstract]

    Both IMT1 (10 μM; 24 h) and CsA (1 μM; 2 h) with VBIT-4 (10 μM; 2 h) inhibits GSDMD oligomerization in PBMCs.

    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    IMT1 is a first-in-class specific and noncompetitive human mitochondrial RNA polymerase (POLRMT) inhibitor. IMT1 causes a conformational change of POLRMT, which blocks substrate binding and transcription in a dose-dependent way in vitro. IMT1 reduces deoxynucleoside triphosphate levels and citric acid cycle intermediates, resulting in a marked depletion of cellular amino acid levels. IMT1 has the potential for mitochondrial transcription disorders related diseases[1].

    In Vitro

    IMT1 (0.00001-10 μM; 0-168 h) has a dose-dependent decrease in cell viability in A2780, A549 and HeLa cells. IMT1 shows a strong decrease in cell viability in about one third of the cancer cell lines, 89 cancer cell lines and primary cells (IMR90 lung fibroblasts and human peripheral blood mononuclear cells (PBMCs)), whereas primary cells remained unresponsive[1].
    ? IMT1 (0.01-10 μM; for 24-200 h) causes a dose-dependent decrease in the levels of mitochondrial transcripts and gradual depletion of mtDNA in HeLa cells. There is a dose-dependent decrease in the levels of subunits (NDUFB8, UQCRC2 and COXI) of respiratory chain complexes I, III and IV[1].
    ? IMT1 reveals a time-dependent and marked increase in the levels of mono- and diphosphate nucleotides that results in a considerable increase in the AMP/ATP ratio and levels of phosphorylated AMPK in A2780 cells[1].
    ? IMT1 severely impairs mtDNA gene expression in A2780 cells that express wild-type POLRMT, whereas cells that express mutant POLRMT (L796Q or L816Q) are resistant[1].
    ? POLRMT is essential for mtDNA transcription and biogenesis of the oxidative phosphorylation (OXPHOS) system[1].

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

    IMT1 Related Antibodies

    Cell Viability Assay[1]

    Cell Line: A2780, A549 and HeLa cells
    Concentration: 0.00001-10 μM
    Incubation Time: 0-168 hours
    Result: Had a dose-dependent decrease in cell viability in A2780, A549 and HeLa cells, but had not cytotoxic to human PBMCs or pooled primary human hepatocytes.
    Molecular Weight

    351.40

    Formula

    C21H21NO4
    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    CC(OC1=CC=C(C(O2)=C1)C(C3=CC=CC=C3C)=CC2=O)C(N(C)C)=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 : 50 mg/mL (142.29 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 2.8458 mL 14.2288 mL 28.4576 mL
    5 mM 0.5692 mL 2.8458 mL 5.6915 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
    =
    Concentration
    ×
    Volume
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    Molecular Weight *

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    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: ≥ 2.5 mg/mL (7.11 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 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: ≥ 2.5 mg/mL (7.11 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.
    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: 98.03%

    COA (250 KB) RP-HPLC (248 KB) MS (69 KB)

    Handling Instructions (2659 KB)
    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 2.8458 mL 14.2288 mL 28.4576 mL 71.1440 mL
    5 mM 0.5692 mL 2.8458 mL 5.6915 mL 14.2288 mL
    10 mM 0.2846 mL 1.4229 mL 2.8458 mL 7.1144 mL
    15 mM 0.1897 mL 0.9486 mL 1.8972 mL 4.7429 mL
    20 mM 0.1423 mL 0.7114 mL 1.4229 mL 3.5572 mL
    25 mM 0.1138 mL 0.5692 mL 1.1383 mL 2.8458 mL
    30 mM 0.0949 mL 0.4743 mL 0.9486 mL 2.3715 mL
    40 mM 0.0711 mL 0.3557 mL 0.7114 mL 1.7786 mL
    50 mM 0.0569 mL 0.2846 mL 0.5692 mL 1.4229 mL
    60 mM 0.0474 mL 0.2371 mL 0.4743 mL 1.1857 mL
    80 mM 0.0356 mL 0.1779 mL 0.3557 mL 0.8893 mL
    100 mM 0.0285 mL 0.1423 mL 0.2846 mL 0.7114 mL
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    IMT1 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:

    IMT12304621-31-4IMT 1IMT-1Oxidative PhosphorylationMitochondrial MetabolismDNA/RNA SynthesismitochondrialRNApolymerasePOLRMTtranscriptiondeoxynucleosidetriphosphatecitricacidintermediatesmtDNArespiratorychainNDUFB8UQCRC2COXIAMP/ATPAMPKOXPHOSInhibitorinhibitorinhibit

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