JavaScript is disabled in your browser. Please enable JavaScript to view this website.
AB254528

MLi-2, LRRK2 inhibitor

Be the first to review this product! Submit a review

|

(6 Publications)

MW 379.5 Da, Purity >98%. Potent and selective LRRK2 inhibitor. Inhibits LRRK2 in cell-free (IC50 = 0.76 nM), cell-based (IC50 = 1.4 nM) and radioligand-binding (IC50 = 3.4 nM) assays. Greater than 295-fold selective against a panel of receptors, channels and over 300 kinases. Oral dosing results in reduced Ser935 phosphorylation of LRRK2 in animal models.
1 Images
Chemical Structure - MLi-2, LRRK2 inhibitor (AB254528)
  • Chemical Structure

Supplier Data

Chemical Structure - MLi-2, LRRK2 inhibitor (AB254528)

2D chemical structure image of ab254528, MLi-2, LRRK2 inhibitor

Key facts

CAS number

1627091-47-7

Purity

>98%

Form

Solid

form

Molecular weight

379.5 Da

Molecular formula

C<sub>2</sub><sub>1</sub>H<sub>2</sub><sub>5</sub>N<sub>5</sub>O<sub>2</sub>

PubChem

78319901

Nature

Synthetic

Solubility

Soluble in DMSO to 100 mM

Biochemical name

MLi-2-Bio-X

Biological description

Potent and selective LRRK2 inhibitor. Inhibits LRRK2 in cell-free (IC50 = 0.76 nM), cell-based (IC50 = 1.4 nM) and radioligand-binding (IC50 = 3.4 nM) assays. Greater than 295-fold selective against a panel of receptors, channels and over 300 kinases. Oral dosing results in reduced Ser935 phosphorylation of LRRK2 in animal models.

Canonical smiles

CC1CN(CC(O1)C)C2=NC=NC(=C2)C3=NNC4=C3C=C(C=C4)OC5(CC5)C

Isomeric smiles

C[C@@H]1CN(C[C@@H](O1)C)C2=NC=NC(=C2)C3=NNC4=C3C=C(C=C4)OC5(CC5)C

InChi

InChI=1S/C21H25N5O2/c1-13-10-26(11-14(2)27-13)19-9-18(22-12-23-19)20-16-8-15(28-21(3)6-7-21)4-5-17(16)24-25-20/h4-5,8-9,12-14H,6-7,10-11H2,1-3H3,(H,24,25)/t13-,14+

InChiKey

ATUUNJCZCOMUKD-OKILXGFUSA-N

IUPAC Name

(2R,6S)-2,6-dimethyl-4-[6-[5-(1-methylcyclopropyl)oxy-1H-indazol-3-yl]pyrimidin-4-yl]morpholine

style
left-column

Complementary Products

Primary Antibodies

AB230261

Anti-RAB10 (phospho T73) antibody [MJF-R21]

20ul selling size|RabMAb|Recombinant|KO Validated

Western blot - Anti-RAB10 (phospho T73) antibody [MJF-R21] (AB230261)

  • 0
  • 0
Primary Antibodies

AB133474

Anti-LRRK2 antibody [MJFF2 (c41-2)]

KO Validated|RabMAb|Recombinant

Western blot - Anti-LRRK2 antibody [MJFF2 (c41-2)] (AB133474)

  • 5
  • 2
Primary Antibodies

AB230260

Anti-RAB8A (phospho T72) antibody [MJF-R20]

RabMAb|Recombinant|20ul selling size

Western blot - Anti-RAB8A (phospho T72) antibody [MJF-R20] (AB230260)

  • 4
  • 3
Primary Antibodies

AB179503

Anti-gamma Tubulin antibody [EPR16793] - Centrosome Marker

RabMAb|Recombinant|Lab Essentials|20ul selling size

Immunocytochemistry/ Immunofluorescence - Anti-gamma Tubulin antibody [EPR16793] - Centrosome Marker (AB179503)

  • 4
  • 3
style
left-column
style
left-column

Properties and storage information

Shipped at conditions
Ambient - Can Ship with Ice
Appropriate short-term storage conditions
-20°C
Appropriate long-term storage conditions
-20°C
style
left-column

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

The protein LRRK2 also known as leucine-rich repeat kinase 2 or dardarin is an enzyme with a molecular weight of approximately 286 kDa. It functions as a kinase meaning it adds phosphate groups to other proteins which affects their activity. LRRK2 is expressed in various tissues but it is highly abundant in the brain especially in regions such as the striatum and cortex. It has a significant role in cellular signaling processes due to its phosphorylation activity.
Biological function summary

LRRK2 interacts with cellular mechanisms by regulating cytoskeletal dynamics autophagy and vesicle trafficking. It is a part of a larger complex that includes other proteins involved in these processes. The kinase activity of LRRK2 plays an essential part in maintaining neuronal health and function. It influences the process of autophagy which is a way cells clean themselves by removing damaged components and recycling them.

Pathways

The action of LRRK2 is central to the mitogen-activated protein kinase (MAPK) and the mammalian target of rapamycin (mTOR) pathways. In these pathways LRRK2 interacts with other proteins such as mTOR and RPS6KB1. It modulates cellular processes like growth proliferation and response to stressors. Its kinase activity affects the phosphorylation state of targets within the pathways hence influencing biological outcomes like survival and apoptosis.

LRRK2 mutations have a significant connection to Parkinson's disease and Crohn's disease. In Parkinson's disease mutated LRRK2 leads to abnormal protein aggregation linking to proteins such as alpha-synuclein. For Crohn's disease LRRK2 influences the immune response and intestinal inflammation. These connections highlight LRRK2's role in the pathogenesis and contribute to understanding these complex disorders.
style
left-column
style
left-column

Product protocols

style
left-column

Publications (6)

Recent publications for all applications. Explore the full list and refine your search

iScience 27:108893 PubMed38313055

2024

Lysosomal stress drives the release of pathogenic α-synuclein from macrophage lineage cells via the LRRK2-Rab10 pathway.

Applications

Unspecified application

Species

Unspecified reactive species

Tetsuro Abe,Tomoki Kuwahara,Shoichi Suenaga,Maria Sakurai,Sho Takatori,Takeshi Iwatsubo

NPJ Parkinson's disease 10:12 PubMed38191886

2024

A potential patient stratification biomarker for Parkinson´s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells.

Applications

Unspecified application

Species

Unspecified reactive species

Yahaira Naaldijk,Belén Fernández,Rachel Fasiczka,Elena Fdez,Coline Leghay,Ioana Croitoru,John B Kwok,Yanisse Boulesnane,Amelie Vizeneux,Eugenie Mutez,Camille Calvez,Alain Destée,Jean-Marc Taymans,Ana Vinagre Aragon,Alberto Bergareche Yarza,Shalini Padmanabhan,Mario Delgado,Roy N Alcalay,Zac Chatterton,Nicolas Dzamko,Glenda Halliday,Javier Ruiz-Martínez,Marie-Christine Chartier-Harlin,Sabine Hilfiker

Journal of peptide science : an official publication of the European Peptide Society 30:e3563 PubMed38135900

2023

Targeting Rab-RILPL interactions as a strategy to downregulate pathogenic LRRK2 in Parkinson's disease.

Applications

Unspecified application

Species

Unspecified reactive species

Krista K Alexander,Yahaira Naaldijk,Rachel Fasiczka,Besma Brahmia,Tiancheng Chen,Sabine Hilfiker,Eileen J Kennedy

The Journal of biological chemistry 299:105192 PubMed37625589

2023

Endogenous Rab38 regulates LRRK2's membrane recruitment and substrate Rab phosphorylation in melanocytes.

Applications

Unspecified application

Species

Unspecified reactive species

Alexandra Unapanta,Farbod Shavarebi,Jacob Porath,Yiyi Shen,Carson Balen,Albert Nguyen,Josh Tseng,Weng Si Leong,Michelle Liu,Pawel Lis,Santiago M Di Pietro,Annie Hiniker

STAR protocols 4:102024 PubMed36856766

2023

Protocol to measure centrosome cohesion deficits mediated by pathogenic LRRK2 in cultured cells using confocal microscopy.

Applications

Unspecified application

Species

Unspecified reactive species

Elena Fdez,Rachel Fasiczka,Antonio Jesús Lara Ordóñez,Belén Fernández,Yahaira Naaldijk,Sabine Hilfiker

iScience 25:104476 PubMed35721463

2022

Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement.

Applications

Unspecified application

Species

Unspecified reactive species

Elena Fdez,Jesús Madero-Pérez,Antonio J Lara Ordóñez,Yahaira Naaldijk,Rachel Fasiczka,Ana Aiastui,Javier Ruiz-Martínez,Adolfo López de Munain,Sally A Cowley,Richard Wade-Martins,Sabine Hilfiker
View all publications
style
left-column
style
left-column
style
right-column

Product promise

We are committed to supporting your work with high-quality reagents, and we're here for you every step of the way. In the unlikely event that one of our products does not perform as expected, you're protected by our Product Promise.
For full details, please see our Terms & Conditions

Please note: All products are 'FOR RESEARCH USE ONLY. NOT FOR USE IN DIAGNOSTIC OR THERAPEUTIC PROCEDURES'.

For licensing inquiries, please contact partnerships@abcam.com