Structure-Guided Discovery of Aminoquinazolines as Brain-Penetrant and Selective LRRK2 Inhibitors

Small-Molecule Kinase Inhibitors for the Treatment of Nononcologic Diseases

(2021) Zhouling Xie et al.   JOURNAL OF MEDICINAL CHEMISTRY

Allosteric Inhibition of Parkinson’s-Linked LRRK2 by Constrained Peptides

(2021) Leah G. Helton et al.   ACS Chemical Biology

Structural analysis of the full-length human LRRK2

(2021) Alexander Myasnikov et al.   CELL

Strategies for Structural Modification of Small Molecules to Improve Blood–Brain Barrier Penetration: A Recent Perspective

(2021) Baichen Xiong et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design and Synthesis of Pyrrolo[2,3-d]pyrimidine-Derived Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Checkpoint Kinase 1 (CHK1)-Derived Crystallographic Surrogate

(2021) Douglas S. Williamson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Understanding LRRK2 kinase activity in preclinical models and human subjects through quantitative analysis of LRRK2 and pT73 Rab10

(2021) Xiang Wang et al.   Scientific Reports

Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-present)

(2020) Xiao Ding et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

An Assessment of LRRK2 Serine 935 Phosphorylation in Human Peripheral Blood Mononuclear Cells in Idiopathic Parkinson’s Disease and G2019S LRRK2 Cohorts

(2020) Shalini Padmanabhan et al.   Journal of Parkinsons Disease

Defining the Neural Kinome: Strategies and Opportunities for Small Molecule Drug Discovery to Target Neurodegenerative Diseases

(2020) Andrea I Krahn et al.   ACS Chemical Neuroscience

Advances in elucidating the function of leucine-rich repeat protein kinase-2 in normal cells and Parkinson's disease

(2020) Matthew Taylor et al.   CURRENT OPINION IN CELL BIOLOGY

The In Situ Structure of Parkinson’s Disease-Linked LRRK2

(2020) Reika Watanabe et al.   CELL

Development and Application of a Transcriptomic Signature of Bioactivation in an Advanced In Vitro Liver Model to Reduce Drug-induced Liver Injury Risk Early in the Pharmaceutical Pipeline

(2020) Wen Kang et al.   TOXICOLOGICAL SCIENCES

Application of a Rat Liver Drug Bioactivation Transcriptional Response Assay Early in Drug Development that informs Chemically Reactive Metabolite formation and Potential for Drug Induced Liver Injury

(2020) James J Monroe et al.   TOXICOLOGICAL SCIENCES

Current and projected future economic burden of Parkinson’s disease in the U.S.

(2020) Wenya Yang et al.   npj Parkinsons Disease

Structure of LRRK2 in Parkinson’s disease and model for microtubule interaction

(2020) C. K. Deniston et al.   NATURE

The Current State-of-the Art of LRRK2-Based Biomarker Assay Development in Parkinson’s Disease

(2020) Hardy J. Rideout et al.   Frontiers in Neuroscience

The tale of proteolysis targeting chimeras (PROTACs) for Leucine‐Rich Repeat Kinase 2 (LRRK2)

(2020) Markella Konstantinidou et al.   ChemMedChem

LRRK2-mediated Rab10 phosphorylation in immune cells from Parkinson's disease patients

(2019) Farzaneh Atashrazm et al.   MOVEMENT DISORDERS

Validation of Human MDR1-MDCK and BCRP-MDCK Cell Lines to Improve the Prediction of Brain Penetration

(2019) Bo Feng et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

In Vitro–In Vivo Extrapolation of Key Transporter Activity at the Blood–Brain Barrier

(2019) Patrick E. Trapa et al.   DRUG METABOLISM AND DISPOSITION

N -Difluorocyclopropyl-Substituted Pyrazoles: Synthesis and Reactivity

(2019) Pavel S. Nosik et al.   EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

Entry of therapeutics into the brain: Influence of exposed polarity calculated in silico and measured in vitro by supercritical fluid chromatography

(2019) Giacomo Russo et al.   INTERNATIONAL JOURNAL OF PHARMACEUTICS

Promiscuity of in Vitro Secondary Pharmacology Assays and Implications for Lead Optimization Strategies

(2019) Dean G. Brown et al.   JOURNAL OF MEDICINAL CHEMISTRY

Brain penetrant kinase inhibitors: Learning from kinase neuroscience discovery

(2018) Yuan Shi et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Prediction of Human Brain Penetration of P-glycoprotein and Breast Cancer Resistance Protein Substrates Using In Vitro Transporter Studies and Animal Models

(2018) Bo Feng et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

LRRK2 kinase in Parkinson's disease

(2018) Dario R. Alessi et al.   SCIENCE

Strategy for Extending Half-life in Drug Design and Its Significance

(2018) Hakan Gunaydin et al.   ACS Medicinal Chemistry Letters

LRRK2 activation in idiopathic Parkinson’s disease

(2018) Roberto Di Maio et al.   Science Translational Medicine

Discovery of potent azaindazole leucine-rich repeat kinase 2 (LRRK2) inhibitors possessing a key intramolecular hydrogen bond – Part 2

(2018) Daniel G.M. Shore et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-2016)

(2017) Paul Galatsis   EXPERT OPINION ON THERAPEUTIC PATENTS

Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1)

(2017) Douglas S. Williamson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a 3-(4-Pyrimidinyl) Indazole (MLi-2), an Orally Available and Selective Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitor that Reduces Brain Kinase Activity

(2017) Jack D. Scott et al.   JOURNAL OF MEDICINAL CHEMISTRY

LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson’s Disease Mouse Model

(2017) Hien Tran Zhao et al.   Molecular Therapy-Nucleic Acids

Selective LRRK2 kinase inhibition reduces phosphorylation of endogenous Rab10 and Rab12 in human peripheral mononuclear blood cells

(2017) Kenneth Thirstrup et al.   Scientific Reports

Improving Drug Design: An Update on Recent Applications of Efficiency Metrics, Strategies for Replacing Problematic Elements, and Compounds in Nontraditional Drug Space

(2016) Nicholas A. Meanwell   CHEMICAL RESEARCH IN TOXICOLOGY

Small Molecule Kinase Inhibitors for the Treatment of Brain Cancer

(2016) Timothy P. Heffron   JOURNAL OF MEDICINAL CHEMISTRY

Integrating in Silico and in Vitro Approaches To Predict Drug Accessibility to the Central Nervous System

(2016) Yan-Yan Zhang et al.   MOLECULAR PHARMACEUTICS

Inhibitor treatment of peripheral mononuclear cells from Parkinson’s disease patients further validates LRRK2 dephosphorylation as a pharmacodynamic biomarker

(2016) G. Perera et al.   Scientific Reports

Chemical Biology of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors

(2015) Anthony A. Estrada et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active, Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

(2015) Qingbei Zeng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Probabilistic Approach to Generating MPOs and Its Application as a Scoring Function for CNS Drugs

(2015) Hakan Gunaydin   ACS Medicinal Chemistry Letters

Leucine-rich repeat kinase 2 inhibitors: a review of recent patents (2011 – 2013)

(2014) Raghava R Kethiri et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

High Throughput Method for the Indirect Detection of Intramolecular Hydrogen Bonding

(2014) Gilles H. Goetz et al.   JOURNAL OF MEDICINAL CHEMISTRY

The role of ligand efficiency metrics in drug discovery

(2014) Andrew L. Hopkins et al.   NATURE REVIEWS DRUG DISCOVERY

Discovery of Highly Potent, Selective, and Brain-Penetrant Aminopyrazole Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors

(2013) Anthony A. Estrada et al.   JOURNAL OF MEDICINAL CHEMISTRY

Can we discover pharmacological promiscuity early in the drug discovery process?

(2012) Jens-Uwe Peters et al.   DRUG DISCOVERY TODAY

Leucine-rich repeat kinase 2 inhibitors: a patent review (2006 – 2011)

(2012) Xianming Deng et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Discovery of Highly Potent, Selective, and Brain-Penetrable Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors

(2012) Anthony A. Estrada et al.   JOURNAL OF MEDICINAL CHEMISTRY

Demystifying Brain Penetration in Central Nervous System Drug Discovery

(2012) Li Di et al.   JOURNAL OF MEDICINAL CHEMISTRY

Development of an enzyme-linked immunosorbent assay for detection of cellular and in vivo LRRK2 S935 phosphorylation

(2012) Lore Delbroek et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

A brief historical perspective: Hodgkin and Huxley

(2012) Christof J. Schwiening   JOURNAL OF PHYSIOLOGY-LONDON

Discovery of a Highly Selective, Brain-Penetrant Aminopyrazole LRRK2 Inhibitor

(2012) Bryan K. Chan et al.   ACS Medicinal Chemistry Letters

Synthesis of gem-Difluorinated Cyclopropanes and Cyclopropenes: Trifluoromethyltrimethylsilane as a Difluorocarbene Source

(2011) Fei Wang et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures

(2011) Mansoureh Hakimi et al.   JOURNAL OF NEURAL TRANSMISSION

Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser910/Ser935, disruption of 14-3-3 binding and altered cytoplasmic localization

(2010) Nicolas Dzamko et al.   BIOCHEMICAL JOURNAL

Membrane Localization of LRRK2 Is Associated with Increased Formation of the Highly Active LRRK2 Dimer and Changes in Its Phosphorylation

(2010) Zdenek Berger et al.   BIOCHEMISTRY

Analysis of Kinase Inhibitor Selectivity using a Thermodynamics-Based Partition Index

(2010) Alan C. Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease

(2010) Mark R. Cookson   NATURE REVIEWS NEUROSCIENCE

The Effect of Breast Cancer Resistance Protein and P-Glycoprotein on the Brain Penetration of Flavopiridol, Imatinib Mesylate (Gleevec), Prazosin, and 2-Methoxy-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)propanoic Acid (PF-407288) in Mice

(2009) L. Zhou et al.   DRUG METABOLISM AND DISPOSITION

A Zone Classification System for Risk Assessment of Idiosyncratic Drug Toxicity Using Daily Dose and Covalent Binding

(2009) S. Nakayama et al.   DRUG METABOLISM AND DISPOSITION

Dependence of Leucine-rich Repeat Kinase 2 (LRRK2) Kinase Activity on Dimerization

(2009) Saurabh Sen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Parkinson's disease

(2009) Andrew J Lees et al.   LANCET

The Impact of IKr Blockade on Medicinal Chemistry Programs

(2008) Ian Bell et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

The Parkinson Disease-associated Leucine-rich Repeat Kinase 2 (LRRK2) Is a Dimer That Undergoes Intramolecular Autophosphorylation

(2008) Elisa Greggio et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study

(2008) Daniel G Healy et al.   LANCET NEUROLOGY