LRRK2-IN1

LRRK2-IN1 : Inhibitor of LRRK2

Structure

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Probe LRRK2-IN1 is in the process of SERP review.

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Information

LRRK2 (Mutant:WT, G2019S)

Inhibitor

~~up to 3 uM~~
Reviewer recommended concentration: 10-20 µM

Probe Availability:

MCULE

In Vitro Validations

Uniprot ID: Q5S007

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 6 nM

Potency Assay: Enzymatic activity of GST-LRRK2[G2019S] (1,326–2,527)

PDB ID for probe-target interaction (3D structure): 5OOT, 5OQ5, 5OQ6, 5VBO, 5WA5, 7L9K, 7LEM, 4YZM

Target aliases:

Leucine-rich repeat serine/threonine-protein kinas ...

DOI Reference: 10.1038/nchembio.538

Uniprot ID: Q5S007

Target Class: Kinase

Target SubClass: TKL

Potency: IC50

Potency Value: 13 nM

Potency Assay: Enzymatic activity of GST-LRRK2 (1,326–2,527)

PDB ID for probe-target interaction (3D structure): 5OOT, 5OQ5, 5OQ6, 5VBO, 5WA5, 7L9K, 7LEM, 4YZM

Target aliases:

Leucine-rich repeat serine/threonine-protein kinas ...

DOI Reference: 10.1038/nchembio.538

Uniprot ID: Q5S007

Target Class: Kinase

Target SubClass: TKL

Potency: Kd

Potency Value: 20 nM

Potency Assay: Binding Assay (Ambit)

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Leucine-rich repeat serine/threonine-protein kinas ...

DOI Reference: 10.1038/nchembio.538

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Off Target: DCLK2

Potency end-point : IC50 45 nM

Potency assay (off target): LRRK2-IN-1 inhibits only 12 kinases among the Ambit 442 diverse kinases panel with a score of less than 10% of the DMSO control at a concentration of 10 μM. (Kinase-binding assays against a panel of 442 distinct kinases using the KINOMEscan methodology (Ambit Biosciences). Radioactivity-based enzymatic assays against a panel of 105 kinases (Dundee profiling) The selectivity score (S (3 μM)) for LRRK2-IN-1, calculated by dividing the number of kinases found to bind with a dissociation constant (Kd < 3 μM) by the total number of kinases tested, is 0.029 (13/442), which represents high selectivity

Potency assay, off target (cells): Activity-based proteomics against 260 kinases using the KiNativ technology (ActivX Biosciences). the selectivity of LRRK2-IN-1 was performed by profiling directly against all kinases detectable in human peripheral blood mononuclear cells (hPBMC, 180 kinases) and mouse brain tissue (195 kinases) using KiNativ.

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(last updated: 21 Feb 2023 )