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Related Concept Videos

Parkinson Disease l: Introduction01:24

Parkinson Disease l: Introduction

Parkinson’s disease is a chronic, progressive neurodegenerative disorder that primarily affects movement. It is characterized by motor symptoms such as resting tremors, muscle rigidity, bradykinesia (slowness of movement), and postural instability. Patients may notice hand tremors at rest, stiffness during movement, or a shuffling gait. In addition to motor features, non-motor symptoms include sleep disturbances, mood and behavioral changes, constipation, and cognitive impairment, all of which...

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Related Experiment Video

Updated: May 17, 2026

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
11:31

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Published on: September 18, 2013

Brain Penetrant LRRK2 Inhibitor.

Hwan Geun Choi1, Jinwei Zhang, Xianming Deng

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA ; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave, SGM 628, Boston, MA 02115, USA.

ACS Medicinal Chemistry Letters
|October 16, 2012
PubMed
Summary
This summary is machine-generated.

A novel compound, HG-10-102-01(4), effectively inhibits leucine-rich repeat kinase 2 (LRRK2) activity, including the Parkinson's disease-associated G2019S mutation. This inhibitor shows promise for Parkinson's disease (PD) therapeutics by reducing LRRK2 phosphorylation in both cellular models and mouse brains.

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Assaying the Kinase Activity of LRRK2 in vitro
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Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation

Published on: March 21, 2020

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Last Updated: May 17, 2026

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
11:31

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Published on: September 18, 2013

Assaying the Kinase Activity of LRRK2 in vitro
06:09

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Published on: January 18, 2012

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation
12:49

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation

Published on: March 21, 2020

Area of Science:

  • Biochemistry
  • Neuroscience
  • Pharmacology

Background:

  • Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are implicated in a subset of Parkinson's disease (PD) cases.
  • LRRK2 is recognized as a potential therapeutic target for Parkinson's disease.

Purpose of the Study:

  • To identify and characterize a potent and selective inhibitor of both wild-type and mutant LRRK2.
  • To evaluate the efficacy of the identified inhibitor in reducing LRRK2 phosphorylation in cellular and in vivo models.

Main Methods:

  • Synthesis and characterization of a novel 2-anilino-4-methylamino-5-chloropyrimidine derivative, designated HG-10-102-01(4).
  • Assessment of compound 4's inhibitory activity against wild-type and G2019S mutant LRRK2 in cellular assays.
  • Measurement of LRRK2 Ser910 and Ser935 phosphorylation levels in cells and mouse brain homogenates after compound administration.

Main Results:

  • Compound 4 demonstrated potent and selective inhibition of both wild-type and G2019S mutant LRRK2.
  • HG-10-102-01(4) significantly inhibited LRRK2 Ser910 and Ser935 phosphorylation in cells at concentrations of 0.1-0.3 µM.
  • This compound was the first reported to inhibit Ser910 and Ser935 phosphorylation in mouse brain following intraperitoneal administration at 50 mg/kg.

Conclusions:

  • HG-10-102-01(4) is a highly effective inhibitor of LRRK2 kinase activity.
  • The compound's ability to reduce LRRK2 phosphorylation in vivo supports its potential as a therapeutic agent for Parkinson's disease.