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Description: Potent and selective LRRK2 inhibitor
Chemical Name: rel-3-[6-[(2R,6S)-2,6-Dimethyl-4-morpholinyl]-4-pyrimidyl]-5-[(1-methylcyclopropyl)oxy]-1H-indazole
Purity: ≥98% (HPLC)
Citations (22)
Reviews (1)
Literature (1)

Biological Activity for MLi-2

MLi-2 is a potent and selective LRRK2 inhibitor (IC50 = 0.76-3.4 nM depending on assay), which exhibits >295-fold selectivity for over 300 kinases and a diverse panel of receptors and ion channels. MLi-2 is centrally bioavailable and active in vivo.

External Portal Information for MLi-2 and the Chemical Probes webpages of the Structural Genomics Consortium are portals that offer independent guidance on the selection and/or application of small molecules for research. The use of MLi-2 is reviewed on and the SGC website.

Compound Libraries for MLi-2

MLi-2 is also offered as part of the Tocriscreen 2.0 Max and Tocriscreen Kinase Inhibitor Library. Find out more about compound libraries available from Tocris.

Technical Data for MLi-2

M. Wt 379.46
Formula C21H25N5O2
Storage Store at -20°C
Purity ≥98% (HPLC)
CAS Number 1627091-47-7
PubChem ID 78319901
Smiles CC1(CC1)OC2=CC=C3C(C(C4=NC=NC(N5C[C@@H](C)O[C@@H](C)C5)=C4)=NN3)=C2

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.

Tocris products are intended for laboratory research use only, unless stated otherwise.

Solubility Data for MLi-2

Solvent Max Conc. mg/mL Max Conc. mM
DMSO 18.97 50

Preparing Stock Solutions for MLi-2

The following data is based on the product molecular weight 379.46. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
0.5 mM 5.27 mL 26.35 mL 52.71 mL
2.5 mM 1.05 mL 5.27 mL 10.54 mL
5 mM 0.53 mL 2.64 mL 5.27 mL
25 mM 0.11 mL 0.53 mL 1.05 mL

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Product Datasheets for MLi-2

Certificate of Analysis / Product Datasheet
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References for MLi-2

References are publications that support the biological activity of the product.

Fell et al (2015) MLi-2, a potent, selective, and centrally active compound for exploring the therapeutic potential and safety of LRRK2 kinase inhibition. J.Pharmacol.Exp.Ther. 355 397 PMID: 26407721

If you know of a relevant reference for MLi-2, please let us know.

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Keywords: MLi-2, MLi-2 supplier, leucine-rich, repeat, kinase, 2, LRRK2, inhibitors, inhibits, potent, neuroprotective, neuronal, injury, parkinson's, parkinsons, 5756, Tocris Bioscience

22 Citations for MLi-2

Citations are publications that use Tocris products. Selected citations for MLi-2 include:

Ole et al (2019) Mitochondrial clearance and maturation of autophagosomes are compromised in LRRK2 G2019S familial Parkinson's disease patient fibroblasts. Hum Mol Genet 28 3232-3243 PMID: 31261377

Henderson et al (2018) LRRK2 activity does not dramatically alter α-synuclein pathology in primary neurons. Acta Neuropathol Commun 6 45 PMID: 29855356

Mark R et al (2022) Lysosomal positioning regulates Rab10 phosphorylation at LRRK2+ lysosomes. Proc Natl Acad Sci U S A 119 e2205492119 PMID: 36256825

Vincent et al (2022) A cell-based GEF assay reveals new substrates for DENN domains and a role for DENND2B in primary ciliogenesis. Sci Adv 8 eabk3088 PMID: 35196081

Sven H et al (2022) Nanobodies as allosteric modulators of Parkinson's disease-associated LRRK2. Proc Natl Acad Sci U S A 119 PMID: 35217606

Sung-Woo et al (2022) LRRK2 Inhibition Mitigates the Neuroinflammation Caused by TLR2-Specific α-Synuclein and Alleviates Neuroinflammation-Derived Dopaminergic Neuronal Loss. Cells 11 PMID: 35269482

Elisa et al (2022) Trafficking of the glutamate transporter is impaired in LRRK2-related Parkinson's disease. Acta Neuropathol 144 81-106 PMID: 35596783

Mark R et al (2022) Directing LRRK2 to membranes of the endolysosomal pathway triggers RAB phosphorylation and JIP4 recruitment. Neurobiol Dis 170 105769 PMID: 35580815

Nicolas et al (2022) WHOPPA Enables Parallel Assessment of Leucine-Rich Repeat Kinase 2 and Glucocerebrosidase Enzymatic Activity in Parkinson's Disease Monocytes. Front Cell Neurosci 16 892899 PMID: 35755775

Catherine et al (2022) DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy. Brain 145 4368-4384 PMID: 36039535

Henderikus et al (2023) Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages. Int J Mol Sci 24 PMID: 36675159

Yuriko et al (2021) Pathogenic LRRK2 regulates ciliation probability upstream of tau tubulin kinase 2 via Rab10 and RILPL1 proteins. Proc Natl Acad Sci U S A 118 PMID: 33653948

John Q et al (2021) LRRK2 Kinase Activity Does Not Alter Cell-Autonomous Tau Pathology Development in Primary Neurons. J Parkinsons Dis 11 1187-1196 PMID: 33720852

Dan et al (2021) Increased LRRK2 kinase activity alters neuronal autophagy by disrupting the axonal transport of autophagosomes. Curr Biol 31 2140-2154.e6 PMID: 33765413

Chelsie A et al (2021) Endosomal traffic and glutamate synapse activity are increased in VPS35 D620N mutant knock-in mouse neurons, and resistant to LRRK2 kinase inhibition. Mol Brain 14 143 PMID: 34530877

Matthias et al (2020) Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease. Mol Cell Proteomics 19 1546-1560 PMID: 33451735

Weidong et al (2020) Parkinson's disease-related Leucine-rich repeat kinase 2 modulates nuclear morphology and genomic stability in striatal projection neurons during aging. Mol Neurodegener 15 12 PMID: 32075681

Shaun et al (2020) LRRK2 mutations impair depolarization-induced mitophagy through inhibition of mitochondrial accumulation of RAB10. Autophagy 16 203-222 PMID: 30945962

Ravindran et al (2020) LRRK2 mediates tubulation and vesicle sorting from lysosomes. Sci Adv 6 PMID: 33177079

Huw R et al (2020) LRRK2 activation controls the repair of damaged endomembranes in macrophages. EMBO J 39 e104494 PMID: 32643832

Matthias et al (2020) Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease. Mol Cell Proteomics 19 1546-1560 PMID: 32601174

Eleanor T et al (2020) Protein synthesis is suppressed in sporadic and familial Parkinson's disease by LRRK2. FASEB J 34 14217-14233 PMID: 32926469

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Reviews for MLi-2

Average Rating: 4 (Based on 1 Review.)

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Good LRRK2 inhibitor.
By Anonymous on 01/27/2023
Assay Type: In Vitro
Species: Rat
Cell Line/Tissue: Primary hippocampal neurons

The drug was incubated at 500 nM to inhibit LRRK2.

Literature in this Area

Tocris offers the following scientific literature in this area to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.

Parkinson's Disease Poster

Parkinson's Disease Poster

Parkinson's disease (PD) causes chronic disability and is the second most common neurodegenerative condition. This poster outlines the neurobiology of the disease, as well as highlighting current therapeutic treatments for symptomatic PD, and emerging therapeutic strategies to delay PD onset and progression.