LRRK2-IN-1   Click here for help

GtoPdb Ligand ID: 9396

Synonyms: LRRK2-IN1 | LRRK2IN1 [2]
PDB Ligand
Compound class: Synthetic organic
Comment: LRRK2-IN-1 is a selective inhibitor of the Parkinson's associated kinase LRRK2 (leucine rich repeat kinase 2) [1]. The compound has limited brain penetrance. LRRK2-IN-1 is used as a pharmacological tool to interrogate the function of LRRK2 in Parkinson's disease.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

LRRK2-IN-1 is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 100.76
Molecular weight 570.31
XLogP 4.66
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES COc1cc(ccc1Nc1ncc2c(n1)n(C)c1ccccc1c(=O)n2C)C(=O)N1CCC(CC1)N1CCN(CC1)C
Isomeric SMILES COc1cc(ccc1Nc1ncc2c(n1)n(C)c1ccccc1c(=O)n2C)C(=O)N1CCC(CC1)N1CCN(CC1)C
InChI InChI=1S/C31H38N8O3/c1-35-15-17-38(18-16-35)22-11-13-39(14-12-22)29(40)21-9-10-24(27(19-21)42-4)33-31-32-20-26-28(34-31)36(2)25-8-6-5-7-23(25)30(41)37(26)3/h5-10,19-20,22H,11-18H2,1-4H3,(H,32,33,34)
InChI Key IWMCPJZTADUIFX-UHFFFAOYSA-N
Bioactivity Comments
LRRK2-IN-1 inhibits activity of the LRRK2 G2019S activating mutation with an IC50 of 6nM [1]. In patient derived lymphoblastoid cells and in mouse in vivo studies, treatment with LRRK2-IN-1 suppresses LRRK2 kinase activity resulting in dephosphorylation of Ser910 and Ser935 and loss of 14-3-3 binding with resultant re-distribution and accumulation of LRRK2 in aggregate fibrillar structures in the cytoplasm.
Kinase profile screening in biochemical assays identifies DCLK2, DCLK1 and MAPK7 as potential off-targets. LRRK1 inhibition could not be evaluated under the same assay conditions as LRRK2 inhibition [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
leucine rich repeat kinase 2 Primary target of this compound Hs Inhibitor Inhibition 8.2 pKi - 2
⤷ pKi 8.2 (Ki 6x10-9 M) [2]
Description: Biochemical assay dissociation constant.
leucine rich repeat kinase 2 Primary target of this compound Hs Inhibitor Inhibition 7.9 pIC50 - 1
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [1]
Description: With 0.1 mM ATP in the assay.