Cat. No.: HY-100411

MLi-2

14 Cited Publications

Customer Review

Based on 14 publication(s) in Google Scholar

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.

Purity: 99.50%
CAS No.: 1627091-47-7
Formula: C₂₁H₂₅N₅O₂
Molecular Weight:379.46

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

MLi-2 Chemical Structure

CAS No.: 1627091-47-7

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Publications (14)
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

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.

Chemical Information

CAS No. 1627091-47-7
Appearance Solid
Molecular Weight 379.46
Formula C₂₁H₂₅N₅O₂
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

Publications (14)

All In Vivo Efficacy StudyFlow CytometryIFCell Imaging/StainingIP

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Journal Impact Factor

Cell Res

Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss. [Abstract]

2025 Jan;35(1):23-44. PMID: 39743632
Nat Commun

Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]

2026 Feb 12;17(1):1214. PMID: 41680175
Nat Commun

Targeting leucine-rich repeat kinase 2 overcomes resistance to oncolytic herpes simplex virus-based therapies in glioblastoma. [Abstract]

2026 Feb 28;17(1):3324. PMID: 41764166
Sci Transl Med

Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson's disease. [Abstract]

2022 Jun 8;14(648):eabj2658. PMID: 35675433
Acta Neuropathol

Mutant LRRK2 exacerbates immune response and neurodegeneration in a chronic model of experimental colitis. [Abstract]

2023 Aug;146(2):245-261. PMID: 37289222

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.
Free Radic Biol Med

Activating Sig-1R inhibits microvascular permeability by reducing LRRK2 expression in lipopolysaccharide-induced acute lung injury. [Abstract]

2025 Jan:226:96-108. PMID: 39542184
J Cell Biol

JIP4 and RILPL1 utilize opposing motor force to dynamically regulate lysosomal tubulation. [Abstract]

2025 Nov 3;224(11):e202404018. PMID: 40990465

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.
Front Immunol

Phosphorylation-driven effector switching of Rab7 and Rab12 by the leucine-rich repeat kinase 1 in mast cells. [Abstract]

2025 Nov 21:16:1709196. PMID: 41357239
Stem Cell Reports

High-content phenotyping of Parkinson's disease patient stem cell-derived midbrain dopaminergic neurons using machine learning classification. [Abstract]

2022 Oct 11;17(10):2349-2364. PMID: 36179692
Exp Neurobiol

Ciliogenesis is Not Directly Regulated by LRRK2 Kinase Activity in Neurons. [Abstract]

2021 Jun 30;30(3):232-243. PMID: 34230223
The University of Alabama at Birmingham

2026.
bioRxiv

2026 Apr 5.
bioRxiv

2024 Mar 31.
bioRxiv

Opposing actions of JIP4 and RILPL1 provide antagonistic motor force to dynamically regulate membrane reformation during lysosomal tubulation/sorting driven by LRRK2. [Abstract]

2024 Apr 3:2024.04.02.587808. PMID: 38903076

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.6353 mL

13.1766 mL

26.3532 mL

5 mM

0.5271 mL

2.6353 mL

5.2706 mL

10 mM

0.2635 mL

1.3177 mL

2.6353 mL

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

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

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

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

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

Stock Solution Working Solution

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

Protocol 3

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

Solubility: ≥ 2 mg/mL (5.27 mM); Clear solution

This protocol yields a clear solution of ≥ 2 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 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.

Protocol 4

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

Solubility: ≥ 2 mg/mL (5.27 mM); Clear solution

This protocol yields a clear solution of ≥ 2 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 (20.0 mg/mL) to 900 μL Corn oil, and mix evenly.

Working 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 Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

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).

Working solution concentration: 0.22 mg/mL

Protocol

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].

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

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (277 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Fell MJ, et al. MLi-2, a Potent, Selective, and Centrally Active Compound for Exploring the Therapeutic Potential and Safety of LRRK2 Kinase Inhibition. J Pharmacol Exp Ther. 2015 Dec;355(3):397-409. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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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MLi-2

Kinase Inhibitor Library

Autophagy Compound Library

Orally Active Compound Library

Chemical Probe Library

Anti-Parkinson's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Targeted Diversity Library

Heterocyclic Compound Library

Highly Selective Inhibitors Library

Serine/Threonine Kinase Inhibitor Library

Bioactive Compound Library Max

Kinase Inhibitor Library Mini

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) MLi-2

Biological Activity

Chemical Information

Publications (14)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

MLi-2

Kinase Inhibitor Library

Autophagy Compound Library

Orally Active Compound Library

Chemical Probe Library

Anti-Parkinson's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Targeted Diversity Library

Heterocyclic Compound Library

Highly Selective Inhibitors Library

Serine/Threonine Kinase Inhibitor Library

Bioactive Compound Library Max

Kinase Inhibitor Library Mini

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) MLi-2

Biological Activity

Chemical Information

Publications (14)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

MLi-2 Related Classifications

Cat. No.: HY-100411