1. Autophagy
  2. LRRK2
  3. MLi-2

MLi-2 est un inhibiteur oralement active et hautement sélectif de LRRK2 avec un IC50 de 0,76 nM. MLi-2 a le potentiel pour la maladie de Parkinson.

MLi-2 ist ein oral aktiver und hochselektiver LRRK2-Inhibitor mit einem IC50 von 0,76 nM. MLi-2 hat das Potenzial für die Parkinson-Krankheit.

MLi-2, a chemical probe, is an orally active and highly selective LRRK2 inhibitor with an IC50 of 0.76 nM. MLi-2 has the potential for Parkinson’s disease.

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

CAS No. : 1627091-47-7

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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Customer Review

Based on 12 publication(s) in Google Scholar

Other Forms of MLi-2:

Top Publications Citing Use of Products

    MLi-2 purchased from MedChemExpress. Usage Cited in: J Cell Biol. 2025 Nov 3;224(11):e202404018.  [Abstract]

    U2OS cells were transfected with HaloTag-LRRK2 for 36 h. Cells were then treated with DMSO, LLOME (1 mM), or LLOME+MLi2 (1 μM, 90 min prior to LLOME incubation) for 2 h before fixation. Cells were then stained for RILPL1 and LAMP2.

    MLi-2 purchased from MedChemExpress. Usage Cited in: J Cell Biol. 2025 Nov 3;224(11):e202404018.  [Abstract]

    Quantification of the RILPL1 lysosomes per cell in the three different conditions. Cells were then treated with DMSO, LLOME (1 mM), or LLOME+MLi2 (1 μM, 90 min prior to LLOME incubation) for 2 h.

    MLi-2 purchased from MedChemExpress. Usage Cited in: J Cell Biol. 2025 Nov 3;224(11):e202404018.  [Abstract]

    HEK293T cells stably expressing GFP-LRRK2 and TMEM192-3xHA were seeded and treated with DMSO, LLOME (1 mM), or LLOME + MLi2 (1 μM, 90 min prior to LLOME incubation) 24 h later. Lysosomes were purified with anti-HA beads following the LYSO-IP technique. Lysosomes were then lysed, and their content was analyzed via immunoblotting.

    MLi-2 purchased from MedChemExpress. Usage Cited in: Acta Neuropathol. 2023 Aug;146(2):245-261.  [Abstract]

    Disease index score evaluation in WT and GS mice treated with placebo or MLi-2 (25 mg/kg/d in diet), after DSS administration.

    MLi-2 purchased from MedChemExpress. Usage Cited in: Acta Neuropathol. 2023 Aug;146(2):245-261.  [Abstract]

    Colonic immunophenotyping by fow cytometry of GS mice treated with MLi-2 (25 mg/kg/d in diet) or placebo, as well as WT mice, after DSS administration.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    MLi-2, a chemical probe, is an orally active and highly selective LRRK2 inhibitor with an IC50 of 0.76 nM. MLi-2 has the potential for Parkinson’s disease[1].

    IC50 & Target

    IC50: 0.76 nM (LRRK2)[1]

    In Vitro

    MLi-2 exhibits exceptional potency in a purified LRRK2 kinase assay in vitro( IC50=0.76 nM), a cellular assay monitoring dephosphorylation of LRRK2 pSer935 LRRK2 (IC50=1.4 nM), and a radioligand competition binding assay (IC50=3.4 nM). MLi-2 has greater than 295-fold selectivity for over 300 kinases in addition to a diverse panel of receptors and ion channels[1].

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

    In Vivo

    Acute oral and subchronic dosing in MLi-2 mice results in dose-dependent central and peripheral target inhibition over a 24-hour period as measured by dephosphorylation of pSer935 LRRK2. Treatment of MitoPark mice with MLi-2 is well tolerated over a 15-week period at brain and plasma exposures. Morphologic changes in the lung, consistent with enlarged type II pneumocytes, are observed in MLi-2-treated MitoPark mice[1].

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

    Molecular Weight

    379.46

    Formula

    C21H25N5O2

    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    C[C@@](C1)([H])O[C@](C)([H])CN1C2=CC(C3=NNC4=CC=C(OC5(C)CC5)C=C43)=NC=N2

    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 (131.77 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 2.6353 mL 13.1766 mL 26.3532 mL
    5 mM 0.5271 mL 2.6353 mL 5.2706 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)

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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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    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:  5% DMSO    40% PEG300    5% Tween-80    50% Saline

      Solubility: 2.87 mg/mL (7.56 mM); Suspended solution; Need ultrasonic

    • Protocol 2

      Add each solvent one by one:  5% DMSO    95% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.87 mg/mL (7.56 mM); Clear solution

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    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:  30% SBE-β-CD in Saline

      Solubility: 5 mg/mL (13.18 mM); Suspension solution; Need ultrasonic

    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: 99.80%

    References
    Animal Administration
    [1]

    Mice: MLi-2 is suspended in 30% Captisol and administered in a volume of 10 mL/kg. Dose calculations are on the basis of active moiety. Mice receive MLi-2 [1-100 mg/kg; by mouth (PO)], or vehicle 1 hour prior to euthanasia by excess CO2. Immediately following euthanasia, mouse brain cortex is dissected and frozen on a steel plate over dry ice for analysis of pSer935 LRRK2 via Western Blot. Plasma and brain samples are collected and frozen for determination of MLi-2 levels by LC-MS/MS[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 2.6353 mL 13.1766 mL 26.3532 mL 65.8831 mL
    5 mM 0.5271 mL 2.6353 mL 5.2706 mL 13.1766 mL
    10 mM 0.2635 mL 1.3177 mL 2.6353 mL 6.5883 mL
    15 mM 0.1757 mL 0.8784 mL 1.7569 mL 4.3922 mL
    20 mM 0.1318 mL 0.6588 mL 1.3177 mL 3.2942 mL
    25 mM 0.1054 mL 0.5271 mL 1.0541 mL 2.6353 mL
    30 mM 0.0878 mL 0.4392 mL 0.8784 mL 2.1961 mL
    40 mM 0.0659 mL 0.3294 mL 0.6588 mL 1.6471 mL
    50 mM 0.0527 mL 0.2635 mL 0.5271 mL 1.3177 mL
    60 mM 0.0439 mL 0.2196 mL 0.4392 mL 1.0981 mL
    80 mM 0.0329 mL 0.1647 mL 0.3294 mL 0.8235 mL
    100 mM 0.0264 mL 0.1318 mL 0.2635 mL 0.6588 mL
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