Aminopurine based JNK inhibitors for the prevention of ischemia reperfusion injury.

  title={Aminopurine based JNK inhibitors for the prevention of ischemia reperfusion injury.},
  author={V{\'e}ronique Plantevin Krenitsky and Mercedes Delgado and Lisa Nadolny and Kiran Sahasrabudhe and Leticia Ayala and Steven S. Clareen and Robert Hilgraf and Ronald Albers and Adam Kois and Kevin S. Hughes and Jonathan Wright and Jacek Nowakowski and Elise A. Sudbeck and Sutapa Ghosh and Sogole Bahmanyar and Philip P. Chamberlain and Jeff Muir and Brian E. Cathers and David A. Giegel and Li Xu and Maria Celeridad and Mehran F. Moghaddam and Oleg G. Khatsenko and Paul Omholt and Jason D. Katz and S. A. Pai and Rachel Fan and Yang Tang and Michael A. Shirley and Brent Benish and Kate Blease and Heather K. Raymon and Shripad S. Bhagwat and Ian R. Henderson and Andrew G Cole and Brydon L. Bennett and Yoshitaka Satoh},
  journal={Bioorganic \& medicinal chemistry letters},
  volume={22 3},
c-Jun N-Terminal Kinases and Their Pharmacological Modulation in Ischemic and Reperfusion Brain Injury
A review of the literature on the role of c-Jun N-terminal kinases (JNK) and their inhibitors in ischemic and reperfusion brain injuries concludes that this task requires a further search for selective JNK3 inhibitors.
Inhibitors of c-Jun N-terminal kinases: an update.
Significant progress in the design of JNK inhibitors displaying selectivity versus other kinases has been achieved within the past 4 years, however, the development of isoform selective JNK inhibitor is still an open task.
Protective Effects of a New C-Jun N-terminal Kinase Inhibitor in the Model of Global Cerebral Ischemia in Rats
The results suggest that the neuroprotective properties of IQ-1S may be mediated by improvement of cerebral microcirculation due to the enhanced vasorelaxation, beneficial effects on blood viscosity, attenuation of the endothelial dysfunction, and antioxidant/antiradical IQ- 1S activity.
Neuroprotective Effects of a Novel Inhibitor of c-Jun N-Terminal Kinase in the Rat Model of Transient Focal Cerebral Ischemia
The findings suggest that IQ-1S inhibits JNK enzymatic activity in the hippocampus and protects against stroke injury when administered in the therapeutic and prophylactic regimen in the rat model of FCI.
JNK inhibitors as anti-inflammatory and neuroprotective agents.
  • P. Graczyk
  • Biology, Chemistry
    Future medicinal chemistry
  • 2013
Recent progress in efforts to design isoform-selective inhibitors is presented and the role of isoform selectivity for efficacy is commented on.
Design and synthesis of 1-aryl-5-anilinoindazoles as c-Jun N-terminal kinase inhibitors.
Design and Synthesis of Highly Potent and Isoform Selective JNK3 Inhibitors: SAR Studies on Aminopyrazole Derivatives
26n was profiled against 464 kinases and was found to be highly selective hitting only seven kinases with >80% inhibition at 10 μM, and showed good solubility, good brain penetration, and good DMPK properties.
c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury
According to reviewed literature, JNKs represent promising therapeutic targets for protection of the brain and the heart against ischemic stroke and myocardial infarction, respectively, but different members of the JNK family exert diverse physiological properties which may not allow for systemic administration of non-specific JNK inhibitors for therapeutic purposes.


Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors.
A series of potent and highly selective JNK inhibitors with good pharmacokinetic profiles are disclosed to disclose a central role in linking obesity and insulin resistance and may be involved in inflammatory and neurological disorders.
Inhibition of c-Jun NH2-Terminal Kinase Activity Improves Ischemia/Reperfusion Injury in Rat Lungs
In conclusion, JNK plays a pivotal role in mediating lung injury caused by I/R, and inhibition of JNK activity has potential as an effective therapeutic strategy for preventing I-R injury during lung transplantation.
JNK mediates hepatic ischemia reperfusion injury.
Past and present course of cardioprotection against ischemia-reperfusion injury.
The present mini-review highlights a short summary of the historical and present course of research into cardioprotection against myocardial I/R injury, suggesting components of the reperfusion injury salvage kinases pathway, protein kinase B, and the extracellular signal-regulated kinases can induce cardiop rotective effect when they are activated during the postischemic reperfusions period.
Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review
  • P. Chatterjee
  • Biology, Medicine
    Naunyn-Schmiedeberg's Archives of Pharmacology
  • 2007
Recent pharmacological developments, which have shown particular promise against experimental renal I-R injury and ischemic ARF, are highlighted, including novel antioxidants and antioxidant enzyme mimetics, nitric oxide andNitric oxide synthase inhibitors, erythropoietin, peroxisome-proliferator-activated receptor agonists, inhibitors of poly(ADP-ribose) polymerase, carbon monoxide-releasing molecules, statins, and adenosine.
Pathway to the clinic: inhibition of P38 MAP kinase. A review of ten chemotypes selected for development.
These results, in addition to proof of concept studies in rheumatoid patients, have established p38 inhibition as an avenue for the future management of pro-inflammatory cytokine based diseases.
Design and synthesis of the first generation of novel potent, selective, and in vivo active (benzothiazol-2-yl)acetonitrile inhibitors of the c-Jun N-terminal kinase.
The in vitro and in vivo anti-inflammatory potential of this new JNK inhibitor was investigated and found to demonstrate efficacy per oral route in an experimental model of rheumatoid arthritis (RA).