ArticleScientific reports2015
Structural basis and biological consequences for JNK2/3 isoform selective aminopyrazoles.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- 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
- Trehalose Attenuates In Vitro Neurotoxicity of 6-Hydroxydopamine by Reducing Oxidative Stress and Activation of MAPK/AMPK Signaling Pathways.International journal of molecular sciences · 2024Article
- Structural Study of Selectivity Mechanisms for JNK3 and p38α with Indazole Scaffold Probing Compounds.Research square · 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
- In vitro and in silico studies of 7'',8''-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors.Scientific reports · 2023Article
- Radiolabeled Aminopyrazoles as Novel Isoform Selective Probes for pJNK3 Quantification.ACS medicinal chemistry letters · 2022Article
- c-JUN n-Terminal Kinase (JNK) Signaling in Autosomal Dominant Polycystic Kidney Disease.Journal of cellular signaling · 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
- c-Jun N-Terminal Kinase Inhibitors as Potential Leads for New Therapeutics for Alzheimer's Diseases.International journal of molecular sciences · 2020Review
- Proposing the Promiscuous Protein Structures in JNK1 and JNK3 for Virtual Screening in Pursuit of Potential Leads.ACS omega · 2020Article
- C-Jun N-terminal kinase inhibitors: Structural insight into kinase-inhibitor complexes.Computational and structural biotechnology journal · 2020Review
- Pyridopyrimidinone Derivatives as Potent and Selective c-Jun N-Terminal Kinase (JNK) Inhibitors.ACS medicinal chemistry letters · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Three JNK isoforms, JNK1, JNK2, and JNK3 have been reported and unique biological function has been ascribed to each. It is unknown if selective inhibition of these isoforms would confer therapeutic or safety benefit. To probe JNK isoform function we designed JNK2/3 inhibitors that have >30-fold selectivity over JNK1. Utilizing site-directed mutagenesis and x-ray crystallography we identified L144 in JNK3 as a key residue for selectivity. To test whether JNK2/3 selective inhibitors protect human dopaminergic neurons against neurotoxin-induced mitochondrial dysfunction, we monitored reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP). The results showed that JNK2/3 selective inhibitors protected against 6-hydroxydopamine-induced ROS generation and MMP depolarization. These results suggest that it was possible to develop JNK2/3 selective inhibitors and that residues in hydrophobic pocket I were responsible for selectivity. Moreover, the findings also suggest that inhibition of JNK2/3 likely contributed to protecting mitochondrial function and prevented ultimate cell death.
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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.