ArticleJournal of medicinal chemistry2014
Design and synthesis of highly potent and isoform selective JNK3 inhibitors: SAR studies on aminopyrazole derivatives.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 64 citations in OpenAlex.
- Identification of Pharmacophore Responsible for the JNK3 Enzyme Inhibition using KPLS-based QSAR Analysis.Central nervous system agents in medicinal chemistry · 2026Article
- Survival motor neuron protein-independent amelioration of spinal muscular atrophy by pharmacological inhibition of c-Jun-NHBrain communications · 2026Article
- Advances in JNK inhibitor development: therapeutic prospects in neurodegenerative diseases and fibrosis.Archives of pharmacal research · 2025Review
- A "Ligand First" Approach toward Selective, Covalent JNK2/3 Inhibitors.Journal of medicinal chemistry · 2025Article
- Regulation of Blood-Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer's Disease and Brain Tumors.Molecules (Basel, Switzerland) · 2025Review
- JNK3 inhibitors as promising pharmaceuticals with neuroprotective properties.Cell adhesion & migration · 2024Review
- Structural Study of Selectivity Mechanisms for JNK3 and p38α with Indazole Scaffold Probing Compounds.Research square · 2024Article
- Structure-aware dual-target drug design through collaborative learning of pharmacophore combination and molecular simulation.Chemical science · 2024Article
- Anti-Inflammatory Activity of Pyrazolo[1,5-Molecules (Basel, Switzerland) · 2024Article
- Development of a Covalent Inhibitor of c-Jun N-Terminal Protein Kinase (JNK) 2/3 with Selectivity over JNK1.Journal of medicinal chemistry · 2023Article
- Radiolabeled Aminopyrazoles as Novel Isoform Selective Probes for pJNK3 Quantification.ACS medicinal chemistry letters · 2022Article
- Identifying New Ligands for JNK3 by Fluorescence Thermal Shift Assays and Native Mass Spectrometry.ACS omega · 2022Article
- Article
- A Perspective on the Development of c-Jun N-terminal Kinase Inhibitors as Therapeutics for Alzheimer's Disease: Investigating Structure through Docking Studies.Biomedicines · 2021Review
- Thiophene-Pyrazolourea Derivatives as Potent, Orally Bioavailable, and Isoform-Selective JNK3 Inhibitors.ACS medicinal chemistry letters · 2021Article
- Identification and neuroprotective evaluation of a potential c-Jun N-terminal kinase 3 inhibitor through structure-based virtual screening and in-vitro assay.Journal of computer-aided molecular design · 2020Article
- C-Jun N-terminal kinase inhibitors: Structural insight into kinase-inhibitor complexes.Computational and structural biotechnology journal · 2020Review
- Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy.Bioorganic & medicinal chemistry letters · 2018Article
- JNK, p38, ERK, and SGK1 Inhibitors in Cancer.Cancers · 2017Article
- Pharmacological Inhibition of c-Jun N-terminal Kinase Reduces Food Intake and Sensitizes Leptin's Anorectic Signaling Actions.Scientific reports · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The c-jun N-terminal kinase 3 (JNK3) is expressed primarily in the brain. Numerous reports have shown that inhibition of JNK3 is a promising strategy for treatment of neurodegeneration. The optimization of aminopyrazole-based JNK3 inhibitors with improved potency, isoform selectivity, and pharmacological properties by structure-activity relationship (SAR) studies utilizing biochemical and cell-based assays, and structure-based drug design is reported. These inhibitors had high selectivity over JNK1 and p38α, minimal cytotoxicity, potent inhibition of 6-OHDA-induced mitochondrial membrane potential dissipation and ROS generation, and good drug metabolism and pharmacokinetic (DMPK) properties for iv dosing. 26n was profiled against 464 kinases and was found to be highly selective hitting only seven kinases with >80% inhibition at 10 μM. Moreover, 26n showed good solubility, good brain penetration, and good DMPK properties. Finally, the crystal structure of 26k in complex with JNK3 was solved at 1.8 Å to explore the binding mode of aminopyrazole based JNK3 inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.