LRRK2-IN-1

SKU: orb1305906

Description

LRRK2-IN-1 is a potent and selective small molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2). It is a valuable research tool for investigating LRRK2's role in Parkinson's disease pathogenesis, enabling both in vitro biochemical assays and in vivo preclinical studies.

Research Area

Cell Biology

Key Properties

• CAS Number: 1234480-84-2
• MW: 570.69
• Purity: 98.00% (May vary between batches)
• Formula: C₃₁H₃₈N₈O₃
• SMILES: COc1cc(ccc1Nc1ncc2N(C)C(=O)c3ccccc3N(C)c2n1)C(=O)N1CCC(CC1)N1CCN(C)CC1
• Target: CDK,LRRK2,Apoptosis
• Solubility: Ethanol:57 mg/mL (99.88 mM);DMSO:245 mg/mL (429.3 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.5 mM)

Bioactivity

• Target IC50:
  LRRK2 (WT):13 nM|DCLK2:45 nM|LRRK2 (G2019S):6 nM
• 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.
• 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. In transgenic C. elegans expressing human R1441C- and G2019S-LRRK2, LRRK2-IN1 rescues the behavioral deficit characteristic of dopaminergic impairment. In mouse fibroblasts, LRRK2-IN1 reduces cell motility. 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.
• Cell Research:
  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.(Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

DCLK1, DCLK2, Apoptosis, LRRK2 (A2016T), LRRK2 (G2019S), LRRK2 (WT), LRRK2 IN 1, LRRK2IN1, LRRK-2-IN-1, LRRK2-IN-1, LRRK2, inhibit, Inhibitor, Leucine-rich repeat kinase 2

Compound Identifiers

PubChem CID

46843906