Catalog # Availability Size / Price Qty
MLi-2 | CAS No. 1627091-47-7 | LRRK2 Inhibitors
1 Image
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%

Product Details
Citations (22)

Biological Activity

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 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.

Technical Data

Soluble to 50 mM in DMSO
Store at -20°C

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.

Background References

  1. LRRK2 kinase plays a critical role in manganese-induced inflammation and apoptosis in microglia
    J Kim, E Pajarillo, A Rizor, DS Son, J Lee, M Aschner, E Lee
    PLoS ONE, 2019;14(1):e0210248.
  2. MLi-2, a potent, selective, and centrally active compound for exploring the therapeutic potential and safety of LRRK2 kinase inhibition.
    Fell et al.
    J.Pharmacol.Exp.Ther., 2015;355:397

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Citations for MLi-2

The citations listed below are publications that use Tocris products. Selected citations for MLi-2 include:

22 Citations: Showing 1 - 10

  1. Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages.
    Authors: Henderikus Et al.
    Int J Mol Sci  2023;24
  2. A cell-based GEF assay reveals new substrates for DENN domains and a role for DENND2B in primary ciliogenesis.
    Authors: Vincent Et al.
    Sci Adv  2022;8:eabk3088
  3. Directing LRRK2 to membranes of the endolysosomal pathway triggers RAB phosphorylation and JIP4 recruitment.
    Authors: Mark R Et al.
    Neurobiol Dis  2022;170:105769
  4. WHOPPA Enables Parallel Assessment of Leucine-Rich Repeat Kinase 2 and Glucocerebrosidase Enzymatic Activity in Parkinson's Disease Monocytes.
    Authors: Nicolas Et al.
    Front Cell Neurosci  2022;16:892899
  5. DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy.
    Authors: Catherine Et al.
    Brain  2022;145:4368-4384
  6. Trafficking of the glutamate transporter is impaired in LRRK2-related Parkinson's disease.
    Authors: Elisa Et al.
    Acta Neuropathol  2022;144:81-106
  7. Lysosomal positioning regulates Rab10 phosphorylation at LRRK2+ lysosomes.
    Authors: Mark R Et al.
    Proc Natl Acad Sci U S A  2022;119:e2205492119
  8. Nanobodies as allosteric modulators of Parkinson's disease-associated LRRK2.
    Authors: Sven H Et al.
    Proc Natl Acad Sci U S A  2022;119
  9. LRRK2 Inhibition Mitigates the Neuroinflammation Caused by TLR2-Specific α-Synuclein and Alleviates Neuroinflammation-Derived Dopaminergic Neuronal Loss.
    Authors: Sung-Woo Et al.
    Cells  2022;11
  10. Increased LRRK2 kinase activity alters neuronal autophagy by disrupting the axonal transport of autophagosomes.
    Authors: Dan Et al.
    Curr Biol  2021;31:2140-2154.e6
  11. Endosomal traffic and glutamate synapse activity are increased in VPS35 D620N mutant knock-in mouse neurons, and resistant to LRRK2 kinase inhibition.
    Authors: Chelsie A Et al.
    Mol Brain  2021;14:143
  12. LRRK2 Kinase Activity Does Not Alter Cell-Autonomous Tau Pathology Development in Primary Neurons.
    Authors: John Q Et al.
    J Parkinsons Dis  2021;11:1187-1196
  13. Pathogenic LRRK2 regulates ciliation probability upstream of tau tubulin kinase 2 via Rab10 and RILPL1 proteins.
    Authors: Yuriko Et al.
    Proc Natl Acad Sci U S A  2021;118
  14. LRRK2 mediates tubulation and vesicle sorting from lysosomes.
    Authors: Ravindran Et al.
    Sci Adv  2020;6
  15. LRRK2 activation controls the repair of damaged endomembranes in macrophages.
    Authors: Huw R Et al.
    EMBO J  2020;39:e104494
  16. Protein synthesis is suppressed in sporadic and familial Parkinson's disease by LRRK2.
    Authors: Eleanor T Et al.
    FASEB J  2020;34:14217-14233
  17. Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease.
    Authors: Matthias Et al.
    Mol Cell Proteomics  2020;19:1546-1560
  18. Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease.
    Authors: Matthias Et al.
    Mol Cell Proteomics  2020;19:1546-1560
  19. LRRK2 mutations impair depolarization-induced mitophagy through inhibition of mitochondrial accumulation of RAB10.
    Authors: Shaun Et al.
    Autophagy  2020;16:203-222
  20. Parkinson's disease-related Leucine-rich repeat kinase 2 modulates nuclear morphology and genomic stability in striatal projection neurons during aging.
    Authors: Weidong Et al.
    Mol Neurodegener  2020;15:12
  21. Mitochondrial clearance and maturation of autophagosomes are compromised in LRRK2 G2019S familial Parkinson's disease patient fibroblasts.
    Authors: Ole Et al.
    Hum Mol Genet  2019;28:3232-3243
  22. LRRK2 activity does not dramatically alter α-synuclein pathology in primary neurons.
    Authors: Henderson Et al.
    Acta Neuropathol Commun  2018;6:45


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