Discovery of XL01126: A Potent, Fast, Cooperative, Selective, Orally Bioavailable, and Blood–Brain Barrier Penetrant PROTAC Degrader of Leucine-Rich Repeat Kinase 2

PROTAC targeted protein degraders: the past is prologue

(2022) Miklós Békés et al.   NATURE REVIEWS DRUG DISCOVERY

Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson’s disease

(2022) Danna Jennings et al.   Science Translational Medicine

PROTAC technology as a novel tool to identify the target of lathyrane diterpenoids

(2022) Yanli Wu et al.   Acta Pharmaceutica Sinica B

Pathogenic LRRK2 regulates ciliation probability upstream of tau tubulin kinase 2 via Rab10 and RILPL1 proteins

(2021) Yuriko Sobu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Parkinson's disease and mitophagy: an emerging role for LRRK2

(2021) Francois Singh et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Increased LRRK2 kinase activity alters neuronal autophagy by disrupting the axonal transport of autophagosomes

(2021) C. Alexander Boecker et al.   CURRENT BIOLOGY

Targeted protein degraders crowd into the clinic

(2021) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

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

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

Impact of Type II LRRK2 inhibitors on signalling and mitophagy

(2021) Anna Tasegian et al.   BIOCHEMICAL JOURNAL

Structural analysis of the full-length human LRRK2

(2021) Alexander Myasnikov et al.   CELL

Pharmacological rescue of impaired mitophagy in Parkinson’s disease-related LRRK2 G2019S knock-in mice

(2021) Francois Singh et al.   eLife

Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases

(2021) Soonsil Hyun et al.   Life-Basel

Discovery of G2019S-Selective Leucine Rich Repeat Protein Kinase 2 inhibitors with in vivo efficacy

(2021) Robert K. Leśniak et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Development of BromoTag: A “Bump-and-Hole”–PROTAC System to Induce Potent, Rapid, and Selective Degradation of Tagged Target Proteins

(2021) Adam G. Bond et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2021) Mitchell H. Keylor et al.   JOURNAL OF MEDICINAL CHEMISTRY

The PROTAC gold rush

(2021) Ken Garber   NATURE BIOTECHNOLOGY

Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

(2021) Satomi Imaide et al.   Nature Chemical Biology

The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences

(2021) Yasset Perez-Riverol et al.   NUCLEIC ACIDS RESEARCH

LRRK2 in Parkinson disease: challenges of clinical trials

(2020) Eduardo Tolosa et al.   Nature Reviews Neurology

LRRK2 inhibitors induce reversible changes in nonhuman primate lungs without measurable pulmonary deficits

(2020) Marco A. S. Baptista et al.   Science Translational Medicine

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

(2020) Reika Watanabe et al.   CELL

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

(2020) C. K. Deniston et al.   NATURE

PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase

(2020) Bikash Adhikari et al.   Nature Chemical Biology

Mitochondrial DNA damage as a potential biomarker of LRRK2 kinase activity in LRRK2 Parkinson’s disease

(2020) C. P. Gonzalez-Hunt et al.   Scientific Reports

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

(2020) Markella Konstantinidou et al.   ChemMedChem

Targeting mitophagy in Parkinson's disease

(2020) Emily H. Clark et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Selective Inhibitors of G2019S-LRRK2 Kinase Activity

(2020) Albert W. Garofalo et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer

(2019) Xin Han et al.   JOURNAL OF MEDICINAL CHEMISTRY

Highly Selective PTK2 Proteolysis Targeting Chimeras to Probe Focal Adhesion Kinase Scaffolding Functions

(2019) Johannes Popow et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cereblon versus VHL: Hijacking E3 ligases against each other using PROTACs

(2019) Miriam Girardini et al.   BIOORGANIC & MEDICINAL CHEMISTRY

SPR-Measured Dissociation Kinetics of PROTAC Ternary Complexes Influence Target Degradation Rate

(2019) Michael J. Roy et al.   ACS Chemical Biology

BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

(2019) William Farnaby et al.   Nature Chemical Biology

Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44

(2019) Nazma Malik et al.   BIOCHEMICAL JOURNAL

Bifunctional chemical probes inducing protein–protein interactions

(2019) Chiara Maniaci et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Targeted protein degradation: expanding the toolbox

(2019) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

Structure-Based Design of a Macrocyclic PROTAC

(2019) Andrea Testa et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Development of a PDEδ-Targeting PROTACs that Impair Lipid Metabolism

(2019) Michael Winzker et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands

(2019) Xin Han et al.   JOURNAL OF MEDICINAL CHEMISTRY

Semi-automated quantitation of mitophagy in cells and tissues

(2019) Lambert Montava-Garriga et al.   MECHANISMS OF AGEING AND DEVELOPMENT

Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand

(2018) Thomas G. McWilliams et al.   Cell Metabolism

Mitochondrial Dysfunction in Parkinson’s Disease: New Mechanistic Insights and Therapeutic Perspectives

(2018) Jin-Sung Park et al.   Current Neurology and Neuroscience Reports

3-Fluoro-4-hydroxyprolines: Synthesis, Conformational Analysis, and Stereoselective Recognition by the VHL E3 Ubiquitin Ligase for Targeted Protein Degradation

(2018) Andrea Testa et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Delineating the role of cooperativity in the design of potent PROTACs for BTK

(2018) Adelajda Zorba et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

LRRK2 kinase in Parkinson's disease

(2018) Dario R. Alessi et al.   SCIENCE

PFE-360-induced LRRK2 inhibition induces reversible, non-adverse renal changes in rats

(2018) Michael Aagaard Andersen et al.   TOXICOLOGY

The genetic landscape of Parkinson's disease

(2018) A. Lunati et al.   REVUE NEUROLOGIQUE

LRRK2 activation in idiopathic Parkinson’s disease

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

Iterative Design and Optimization of Initially Inactive Proteolysis Targeting Chimeras (PROTACs) Identify VZ185 as a Potent, Fast, and Selective von Hippel–Lindau (VHL) Based Dual Degrader Probe of BRD9 and BRD7

(2018) Vittoria Zoppi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Addressing Kinase-Independent Functions of Fak via PROTAC-Mediated Degradation

(2018) Philipp M. Cromm et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

The Emerging Evidence of the Parkinson Pandemic

(2018) E. Ray Dorsey et al.   Journal of Parkinsons Disease

Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease

(2017) Andrew B. West   EXPERIMENTAL NEUROLOGY

Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase: Structure–Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298)

(2017) Pedro Soares et al.   JOURNAL OF MEDICINAL CHEMISTRY

Impact of Target Warhead and Linkage Vector on Inducing Protein Degradation: Comparison of Bromodomain and Extra-Terminal (BET) Degraders Derived from Triazolodiazepine (JQ1) and Tetrahydroquinoline (I-BET726) BET Inhibitor Scaffolds

(2017) Kwok-Ho Chan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Protac-Induced Protein Degradation in Drug Discovery: Breaking the Rules or Just Making New Ones?

(2017) Ian Churcher   JOURNAL OF MEDICINAL CHEMISTRY

The SH-SY5Y cell line in Parkinson’s disease research: a systematic review

(2017) Helena Xicoy et al.   Molecular Neurodegeneration

Structural basis of PROTAC cooperative recognition for selective protein degradation

(2017) Morgan S Gadd et al.   Nature Chemical Biology

Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

(2017) Martin Steger et al.   eLife

The Perseus computational platform for comprehensive analysis of (prote)omics data

(2016) Stefka Tyanova et al.   NATURE METHODS

Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition

(2016) Julianty Frost et al.   Nature Communications

Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

(2016) Martin Steger et al.   eLife

Applications of Fluorine in Medicinal Chemistry

(2015) Eric P. Gillis et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Preclinical Profiling of 3-[4-(Morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a Highly Potent, Selective, Brain Penetrant, and in Vivo Active LRRK2 Kinase Inhibitor

(2014) Jaclyn L. Henderson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Abrogation of  -synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats

(2014) J. P. L. Daher et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Loss of iron triggers PINK1/Parkin-independent mitophagy

(2013) George F G Allen et al.   EMBO REPORTS

Dissecting Fragment-Based Lead Discovery at the von Hippel-Lindau Protein:Hypoxia Inducible Factor 1α Protein-Protein Interface

(2012) Inge Van Molle et al.   CHEMISTRY & BIOLOGY

Brain Penetrant LRRK2 Inhibitor

(2012) Hwan Geun Choi et al.   ACS Medicinal Chemistry Letters

Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2

(2011) Xianming Deng et al.   Nature Chemical Biology

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease

(2010) Byoung Dae Lee et al.   NATURE MEDICINE

MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification

(2008) Jürgen Cox et al.   NATURE BIOTECHNOLOGY

Fluorine in medicinal chemistry

(2007) Sophie Purser et al.   CHEMICAL SOCIETY REVIEWS