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  2. LRRK2

MLi-2 

Cat. No.: HY-100411 Purity: 99.66%
Handling Instructions

MLi-2 is an a potent, highly selective, orally available, brain penetrant inhibitor of LRRK2 with an IC50 of 0.76 nM.

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

MLi-2 Chemical Structure

MLi-2 Chemical Structure

CAS No. : 1627091-47-7

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 198 In-stock
Estimated Time of Arrival: December 31
5 mg USD 180 In-stock
Estimated Time of Arrival: December 31
10 mg USD 276 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1176 In-stock
Estimated Time of Arrival: December 31
100 mg USD 1980 In-stock
Estimated Time of Arrival: December 31
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500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

MLi-2 is an a potent, highly selective, orally available, brain penetrant inhibitor of LRRK2 with an IC50 of 0.76 nM.

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].

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].

Solvent & Solubility
In Vitro: 

DMSO : ≥ 26 mg/mL (68.52 mM)

*"≥" means soluble, but saturation unknown.

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
10 mM 0.2635 mL 1.3177 mL 2.6353 mL
*Please refer to the solubility information to select the appropriate solvent.
References
Kinase Assay
[1]

MLi-2 dose response is prepared by diluting a 10 mM stock of MLi-2 to a top concentration of 98 μM in 100% DMSO followed by serial dilution by 1:2.15 in DMSO nine times. Four hundred nanoliters of each dilution is spotted via a Labcyte Echo onto a 384-well black-sided plate followed by 10 μL of a 2.5 nM enzyme solution in 1xassay buffer. Following a 30-minute incubation at room temperature, the kinase reaction is started with the addition of 10 μL of 800 nM fluorescein-labeled LRRKtide peptide substrate and 186 μM ATP solution in 1x assay buffer. The reaction is allowed to progress at 25°C for 1 hour. The reaction is then stopped by the addition of 20 μL of TR-FRET Dilution Buffer containing 4 nM Tb-labeled anti-phospho LRRKtide antibody and 20 mM EDTA. After an incubation of 1 hour at room temperature, the plate is read on 340, 520 and 495 nm[1].

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

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
Molecular Weight

379.46

Formula

C₂₁H₂₅N₅O₂

CAS No.

1627091-47-7

SMILES

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

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Purity: 99.66%

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Product Name:
MLi-2
Cat. No.:
HY-100411
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MLi-2

Cat. No.: HY-100411