Home Autophagy LRRK2 inhibitor LRRK2-IN-1 For research use only.

LRRK2-IN-1

LRRK2-IN-1 is a potent and selective LRRK2 inhibitor with IC50 of 6 nM and 13 nM for LRRK2 (G2019S) and LRRK2 (WT), respectively.

LRRK2-IN-1 Chemical Structure

LRRK2-IN-1 Chemical Structure

CAS No. 1234480-84-2

Purity & Quality Control

Batch: S758401 DMSO]100 mg/mL]false]Ethanol]100 mg/mL]false]Water]Insoluble]false Purity: 99.61%
99.61

LRRK2-IN-1 Related Products

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HEK293 cells Function assay Inhibition of LRRK2 G2019S mutant expressed in HEK293 cells using nictide and ATP as substrate, IC50=0.006 μM 22335897
HEK293 cells Function assay 0.03-3 μM 90 mins Inhibition of wild-type LRRK2 phosphorylation at Ser935 expressed in HEK293 cells at 0.03 to 3 uM after 90 mins by immunoblot analysis 22335897
lymphoblastoid cells Function assay 0.03 to 3 uM 90 mins Inhibition of LRRK2 in human lymphoblastoid cells assessed as inhibition of Ser910 autophosphorylation at 0.03 to 3 uM after 90 mins by immunoblot method 22863203
Click to View More Cell Line Experimental Data

Biological Activity

Description LRRK2-IN-1 is a potent and selective LRRK2 inhibitor with IC50 of 6 nM and 13 nM for LRRK2 (G2019S) and LRRK2 (WT), respectively.
Targets
LRRK2 (G2019S) [1]
(Cell-free assay)		 LRRK2 (WT) [1]
(Cell-free assay)		 DCLK2 [1]
(Cell-free assay)
6 nM 13 nM 45 nM
In vitro
In vitro In HEK 293 cells stably expressing GFP-LRRK2[G2019S], LRRK2-IN-1 alters the cytoplasmic localization of LRRK2. In human-derived neuroblastoma SHSY5Y cells and mouse Swiss 3T3 cells, LRRK2-IN-1 induces a similar dose-dependent Ser910 and Ser935 dephosphorylation and loss of 14-3-3 binding to endogenous LRRK2. [1] In transgenic C. elegans expressing human R1441C- and G2019S-LRRK2, LRRK2-IN1 rescues the behavioral deficit characteristic of dopaminergic impairment. [2] In mouse fibroblasts, LRRK2-IN1 reduces cell motility. [3] In AsPC-1 and HCT116 cell lines, LRRK2-IN-1 shows anti-proliferative and pro-apoptotic properties, induces G1 and G2/M cell cycle arrest and inhibits DCLK1 mRNA and protein expression. [4]
Kinase Assay IC50 determination
Active GST-LRRK2 (1326-2527), GST-LRRK2 [G2019S] (1326-2527), GST-LRRK2 [A2016T] (1326-2527) and GST-LRRK2 [A2016T+G2019S] (1326-2527) enzyme is purified with glutathione sepharose from HEK293 cell lysate 36 h following transient transfection of the appropriate cDNA constructs. Peptide kinase assays, performed in duplicate, are set up in a total volume of 40 µL containing 0.5 µg LRRK2 kinase (which at approximately 10% purity gives a final concentration of 8 nM) in 50 mM Tris/HCl, pH 7.5, 0.1 mM EGTA, 10 mM MgCl2, 20 µM Nictide, 0.1 µM [γ-32P]ATP (~500 cpm/pmol) and the indicated concentrations of inhibitor dissolved in DMSO. After incubation for 15 min at 30 °C, reactions are terminated by spotting 35 µL of the reaction mix onto P81 phosphocellulose paper and immersion in 50 mM phosphoric acid. Samples are washed extensively and the incorporation of [γ-32P]ATP into Nictide is quantified by Cerenkov counting. IC50 values are calculated with GraphPad Prism using non-linear regression analysis.
Cell Research Cell lines HCT116, and AsPC-1 cells
Concentrations 20 μM
Incubation Time 48 h
Method Cells are seeded into a 96-well tissue culture plate in triplicate. The cells are cultured in the presence of LRRK2-IN-1 with DMSO as a vehicle at 0, 0.31, 0.63, 1, 2, and 5, 10, and 20 μM. 48 h post treatment, 10 μL of TACS MTT Reagent (RND Systems) is added to each well and the cells are incubated at 37°C until dark crystalline precipitate became visible in the cells. 100 μL of 266 mM NH4OH in DMSO is then added to the wells and placed on a plate shaker at low speed for 1 minute. After shaking, the plate is allowed to incubate for 10 minutes protected from light and the OD550 for each well is read using a microplate reader. The results are averaged and calculated as a percentage of the DMSO (vehicle) control +/- the standard error of the mean.
In Vivo
In vivo In wild type male C57BL/6 mice, LRRK2-IN-1 (100 mg/kg, i.p.) inhibits Ser910 and Ser935 dephosphorylation of LRRK2 in the kidney, while no effects in the brain. [1]
Animal Research Animal Models Wild type male C57BL/6 mice
Dosages 100 mg/kg
Administration i.p.

Chemical Information & Solubility

Molecular Weight 570.69 Formula

C31H38N8O3
CAS No. 1234480-84-2 SDF Download LRRK2-IN-1 SDF
Smiles CN1CCN(CC1)C2CCN(CC2)C(=O)C3=CC(=C(C=C3)NC4=NC=C5C(=N4)N(C6=CC=CC=C6C(=O)N5C)C)OC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (175.22 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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