1. Autophagy
  2. LRRK2

LRRK2-IN-1 

Cat. No.: HY-10875 Purity: 99.38%
Handling Instructions

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.

For research use only. We do not sell to patients.

LRRK2-IN-1 Chemical Structure

LRRK2-IN-1 Chemical Structure

CAS No. : 1234480-84-2

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 152 In-stock
Estimated Time of Arrival: December 31
10 mg USD 138 In-stock
Estimated Time of Arrival: December 31
50 mg USD 528 In-stock
Estimated Time of Arrival: December 31
100 mg USD 900 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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    LRRK2-IN-1 purchased from MCE. Usage Cited in: Mol Pharm. 2018 Aug 6;15(8):3252-3259.

    Western blot analysis the expression of c-Myc and DCLK1 treated with or without LRRK2-IN-1 in Jurkat cells.

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    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    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.

    IC50 & Target

    IC50: 13 nM (WT), 6 nM (G2019S)

    In Vitro

    Wild-type and G2019S transduction results in 2.5 fold higher TR-FRET signal which can be inhibited by LRRK2-IN-1 in a dose-dependent manner with IC50 values of 0.08 µM and 0.03 µM, respectively[1]. LRRK2-IN-1 possessed an IC50 of 45 nM for inhibition of DCLK2 and exhibits an IC50 of greater than 1 µM when evaluated in biochemical assays for AURKB, CHEK2, MKNK2, MYLK, NUAK1, and PLK1. LRRK2-IN-1 is confirmed to inhibit MAPK7 with an EC50 of 160 nM. LRRK2-IN-1 induces a dose dependent inhibition of Ser910 and Ser935 phosphorylation accompanied by loss of 14-3-3 binding to both wild type LRRK2 and LRRK2[G2019S] stably transfected into HEK293 cells[2]. LRRK2-IN-1 is moderately cytotoxic with IC50 of 49.3 µM in HepG2 cells. LRRK2-IN-1 exhibits genotoxicity in the presence and absence of S9 at 15.6 and 3.9 µM, respectively[3]. LRRK2-IN-1 inhibits proliferation, migration, and induces cell death with hallmarks of apoptosis of HCT116 and AsPC-1 cells[4].

    In Vivo

    LRRK2-IN-1 (100 mg/kg, i.p.) induces dephosphorylation of LRRK2 in the kidney of the mice[2]. Peritumoral injection of LRRK2-IN-1 (100 mg/kg) results in a significant decrease in tumor volume and weight of AsPC-1 tumor xenografts[4].

    Solvent & Solubility
    In Vitro: 

    10 mM in DMSO

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.7523 mL 8.7613 mL 17.5226 mL
    5 mM 0.3505 mL 1.7523 mL 3.5045 mL
    10 mM 0.1752 mL 0.8761 mL 1.7523 mL
    *Please refer to the solubility information to select the appropriate solvent.
    References
    Kinase Assay
    [2]

    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.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [4]

    Cells (104 cells per well) 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 is added to each well and the cells are incubated at 37°C until dark crystalline precipitate become 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.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    LRRK2-IN-1 is dissolved in Captisol and administered by intraperitoneal injection into wild type male C57BL/6 mice at a dose of 100 mg/kg. Control mice are injected with an equal volume of Captisol. At 1 and 2 h time points, mice are extinguwashed by cervical dislocation and kidney and brain tissue rapidly dissected and snap-frozen in liquid nitrogen.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    570.69

    Formula

    C₃₁H₃₈N₈O₃

    CAS No.

    1234480-84-2

    SMILES

    O=C(C1=CC(OC)=C(NC2=NC=C3C(N(C4=C(C(N3C)=O)C=CC=C4)C)=N2)C=C1)N5CCC(CC5)N6CCN(CC6)C

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.38%

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    Product Name:
    LRRK2-IN-1
    Cat. No.:
    HY-10875
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    LRRK2-IN-1

    Cat. No.: HY-10875