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Chemical Structure| 1627091-47-7 Chemical Structure| 1627091-47-7

Structure of MLi-2
CAS No.: 1627091-47-7

Chemical Structure| 1627091-47-7

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MLi-2 is a highly potent, and selective LRRK2 kinase inhibitor with central nervous system activity.

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Product Details of MLi-2

CAS No. :1627091-47-7
Formula : C21H25N5O2
M.W : 379.46
SMILES Code : CC1(OC2=CC3=C(NN=C3C4=CC(N5C[C@H](C)O[C@H](C)C5)=NC=N4)C=C2)CC1
MDL No. :MFCD30536362
InChI Key :ATUUNJCZCOMUKD-OKILXGFUSA-N
Pubchem ID :78319901

Safety of MLi-2

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P332+P313-P337+P313-P362-P403+P233-P405-P501

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Human Embryonic Kidney 293 cells (HEK293) 1 μM 4 hours To investigate the effect of MLi-2 on 14-3-3 binding to LRRK2. Results showed that 1 μM MLi-2 completely ablated 14-3-3 binding and Ser935 phosphorylation. Biochem J. 2021 Oct 15;478(19):3555-3573
Mouse Embryonic Fibroblasts (MEFs) 100 nM 2 hours To evaluate the inhibitory effect of MLi-2 on LRRK2-mediated Rab10 phosphorylation. Results showed that 1 μM MLi-2 reduced Rab10 and Rab12 phosphorylation to almost background levels. Biochem J. 2021 Oct 15;478(19):3555-3573
HEK293FT cells 1μM 90 minutes To evaluate the inhibitory effect of MLi-2 on LRRK2 kinase activity, results showed that MLi-2 significantly reduced Rab10 phosphorylation levels. Mol Neurodegener. 2021 Mar 19;16(1):17
primary hippocampal neurons 10 nM or 30 nM 7 days Reduced LRRK2 kinase activity increases α-synuclein overlap with presynaptic markers in primary neurons Acta Neuropathol Commun. 2021 Nov 8;9(1):180
Wild-type and G2019S-LRRK2 mouse microglia 1 µM 24 hours To investigate the inhibitory effect of MLi-2 on LRRK2 kinase activity and its impact on gene expression. Results showed that MLi-2 significantly inhibited zymosan-induced LRRK2 Ser935 phosphorylation. Cells. 2023 Dec 26;13(1):53

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice G2019S LRRK2 knock-in (KI) mice In-diet administration 60 mg/kg/day Once daily for 10 weeks To evaluate the molecular effects of chronic LRRK2 kinase inhibition, results showed that MLi-2 significantly reduced S1292 LRRK2 and S106 Rab12 phosphorylation levels and affected endolysosomal and mitochondrial pathways. Mol Neurodegener. 2021 Mar 19;16(1):17
Mice LRRK2G2019S knock-in mice Dietary administration 0, 10, or 60 mg/kg/day Continuous for 3-6 months To assess the impact of LRRK2 kinase inhibition on tau pathology progression. Results showed that LRRK2 kinase inhibition reversed tau pathology progression in LRRK2G2019S mice but had minimal effect in wild-type mice. Transl Neurodegener. 2024 Mar 4;13(1):13
Mice Parkinson's disease model Dietary administration 30 mg/kg/day Continuous for 3 months To assess the effect of MLi-2 on α-synuclein pathology and neuron death. Results showed MLi-2 significantly reduced LRRK2 kinase activity but did not improve motor function, α-synuclein pathology accumulation, or neuron loss. Acta Neuropathol Commun. 2019 Feb 26;7(1):28
Mice Vps35 p.D620N knock-in (VKI) mice Intraperitoneal injection 5 mg/kg Once daily for 7 days MLi-2 significantly abolished Rab phosphorylation in VKIs with a clear interaction between treatment and genotype, further supporting that hyperphosphorylation of Rab proteins in VKIs are LRRK2 kinase dependent. NPJ Parkinsons Dis. 2023 Dec 18;9(1):167

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.64mL

0.53mL

0.26mL

13.18mL

2.64mL

1.32mL

26.35mL

5.27mL

2.64mL

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