ArticleACS chemical biology2013
A small molecule bidentate-binding dual inhibitor probe of the LRRK2 and JNK kinases.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- c-Jun N-terminal kinase signaling in aging.Frontiers in aging neuroscience · 2024Review
- Article
- Role of c-Jun-N-Terminal Kinase in Pregnane X Receptor-Mediated Induction of Human Cytochrome P4503A4 In Vitro.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Uncovering the Signaling Pathway behind Extracellular Guanine-Induced Activation of NO System: New Perspectives in Memory-Related Disorders.Frontiers in pharmacology · 2018Article
- Pyridopyrimidinone Derivatives as Potent and Selective c-Jun N-Terminal Kinase (JNK) Inhibitors.ACS medicinal chemistry letters · 2015Article
- Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors.Journal of medicinal chemistry · 2015Article
- Structural basis and biological consequences for JNK2/3 isoform selective aminopyrazoles.Scientific reports · 2015Article
- Design and synthesis of highly potent and isoform selective JNK3 inhibitors: SAR studies on aminopyrazole derivatives.Journal of medicinal chemistry · 2014Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Both JNK and LRRK2 are associated with Parkinson's disease (PD). Here we report a reasonably selective and potent kinase inhibitor (compound 6) that bound to both JNK and LRRK2 (a dual inhibitor). A bidentate-binding strategy that simultaneously utilized the ATP hinge binding and a unique protein surface site outside of the ATP pocket was applied to the design and identification of this kind of inhibitor. Compound 6 was a potent JNK3 and modest LRRK2 dual inhibitor with an enzyme IC50 value of 12 nM and 99 nM (LRRK2-G2019S), respectively. Compound 6 also exhibited good cell potency, inhibited LRRK2:G2019S-induced mitochondrial dysfunction in SHSY5Y cells, and was demonstrated to be reasonably selective against a panel of 116 kinases from representative kinase families. Design of such a probe molecule may help enable testing if dual JNK and LRRK2 inhibitions have added or synergistic efficacy in protecting against neurodegeneration in PD.
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Registered trials
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