These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Highly selective c-Jun N-terminal kinase (JNK) 2 and 3 inhibitors with in vitro CNS-like pharmacokinetic properties prevent neurodegeneration.
    Author: Probst GD, Bowers S, Sealy JM, Truong AP, Hom RK, Galemmo RA, Konradi AW, Sham HL, Quincy DA, Pan H, Yao N, Lin M, Tóth G, Artis DR, Zmolek W, Wong K, Qin A, Lorentzen C, Nakamura DF, Quinn KP, Sauer JM, Powell K, Ruslim L, Wright S, Chereau D, Ren Z, Anderson JP, Bard F, Yednock TA, Griswold-Prenner I.
    Journal: Bioorg Med Chem Lett; 2011 Jan 01; 21(1):315-9. PubMed ID: 21112785.
    Abstract:
    In this Letter, we describe the discovery of selective JNK2 and JNK3 inhibitors, such as 10, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs, p38α and ERK2. Substitution of the naphthalene ring affords an isoform selective JNK3 inhibitor, 30, with approximately 10-fold selectivity over both JNK1 and JNK2. A naphthalene ring penetrates deep into the selectivity pocket accounting for the differentiation amongst the kinases. Interestingly, the gatekeeper Met146 sulfide interacts with the naphthalene ring in a sulfur-π stacking interaction. Compound 38 ameliorates neurotoxicity induced by amyloid-β in human cortical neurons. Lastly, we demonstrate how to install propitious in vitro CNS-like properties into these selective inhibitors.
    [Abstract] [Full Text] [Related] [New Search]