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MLi-2 LRRK2 inhibitor

Name: MLi-2
Brand: Selleck Chemicals
SKU: S9694
Availability: InStock
Rating: 5 (1 reviews)

Cat.No.S9694

MLi-2 is an orally active and highly selective inhibitor of LRRK2. This compound exhibits exceptional potency in a purified LRRK2 kinase assay in vitro with IC50 of 0.76 nM, a cellular assay monitoring dephosphorylation of LRRK2 pSer935 LRRK2 with IC50 of 1.4 nM, and a radioligand competition binding assay with IC50 of 3.4 nM.

Chemical Structure

Molecular Weight: 379.46

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Quality Control

Batch: Purity: 99.79%

99.79

Related Targets	CXCR Autophagy Nrf2 Mitophagy ULK FKBP Heme Oxygenase LC3 cGAS Cell wall
Other LRRK2 Products	LRRK2-IN-1 PFE-360 GNE-0877 (DNL201) GNE-7915 GSK2578215A Phospho-LRRK2 (Ser955) Antibody [F1M24] LRRK2 Antibody [P18P16] CZC-54252 GNE-9605 CZC-25146

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
SH-SY5Y	Function assay		90 mins		Inhibition LRRK2 G2019S mutant Ser935 phosphorylation in human SH-SY5Y cells after 90 mins by Western blot analysis, IC50 = 0.0048 μM.	28245354
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 76 mg/mL (200.28 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.900mg/ml (5.01mM)	Taking the 1 mL working solution as an example, add 50 μL of 38 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.900mg/ml (5.01mM)	Taking the 1 mL working solution as an example, add 50 μL of 38 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	379.46	Formula	C₂₁H₂₅N₅O₂	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	1627091-47-7	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1CN(CC(C)O1)C2=CC(=NC=N2)C3=N[NH]C4=CC=C(OC5(C)CC5)C=C34

Mechanism of Action

Targets/IC₅₀/Ki	LRRK2 (purified LRRK2 kinase assay in vitro) 0.76 nM LRRK2 (cellular assay monitoring dephosphorylation of LRRK2 pSer935 LRRK2) 1.4 nM LRRK2 (radioligand competition binding assay) 3.4 nM
In vitro	MLi-2 is a structurally novel, highly potent, and selective LRRK2 kinase inhibitor with central nervous system activity. This compound 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). It has greater than 295-fold selectivity for over 300 kinases in addition to a diverse panel of receptors and ion channels.
In vivo	Acute oral and subchronic dosing in MLi-2 mice resulted in dosedependent central and peripheral target inhibition over a 24-hour period as measured by dephosphorylation of pSer935 LRRK2. Treatment of MitoPark mice with this compound is well tolerated over a 15-week period at brain and plasma exposures >100× the in vivo plasma IC50 for LRRK2 kinase inhibition as measured by pSer935 dephosphorylation. Morphologic changes in the lung, consistent with enlarged type II pneumocytes, are observed in this compound-treated MitoPark mice.
References	[1] https://pubmed.ncbi.nlm.nih.gov/26407721/

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