Pyrazolo[4,3-c]isoquinolines as potential inhibitors of NF-kappaB activation.

Arthritis, Rheumatoid/metabolism; Hela Cells; Humans; Isoquinolines/antagonists & inhibitors; MAP Kinase Kinase Kinases/drug effects/physiology; NF-kappa B/antagonists & inhibitors/physiology; Pyrazoles/antagonists & inhibitors; Recombinant Proteins; Signal Transduction/drug effects/physiology; Structure-Activity Relationship

Abstract :

[en] In this work, we aimed to build a 3D-model of NIK and to study the binding of pyrazolo[4,3-c]isoquinolines with a view to highlight the structural elements responsible for their inhibitory potency. However, in the course of this work, we unexpectedly found that the pyrazolo[4,3-c]isoquinolines initially reported as NIK inhibitors were neither inhibitors of this enzyme nor of the alternative NF-kappaB pathway, but were in fact inhibitors of another kinase, the TGF-beta activated kinase 1 (TAK1) which is involved in the classical NF-kappaB pathway.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Mortier, Jeremie

Frederick, Raphael

Ganeff, Corinne

Remouchamps, Caroline ; Université de Liège - ULiège > GIGA-R : Virologie - Immunologie

Talaga, Patrice

Pochet, Lionel

Wouters, Johan

Piette, Jacques ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research

Dejardin, Emmanuel ; Université de Liège - ULiège > GIGA-R : Virologie - Immunologie

Masereel, Bernard

Language :

English

Title :

Pyrazolo[4,3-c]isoquinolines as potential inhibitors of NF-kappaB activation.

Publication date :

2010

Journal title :

Biochemical Pharmacology

ISSN :

0006-2952

eISSN :

1873-2968

Publisher :

Elsevier Science, Oxford, United Kingdom

Volume :

Issue :

Pages :

1462-72

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 05 March 2015

Statistics

Number of views

48 (1 by ULiège)

Number of downloads

1 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

McInnes I.B., and Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7 6 (2007) 429-442
Martinon F., and Tschopp J. NLRs join TLRs as innate sensors of pathogens. Trends Immunol 26 8 (2005) 447-454
Yamaguchi K., Shirakabe T., Shibuya H., Irie K., Oishi I., Ueno N., et al. Identification of a member of the Mapkkk family as a potential mediator of Tgf-Beta signal-transduction. Science 270 5244 (1995) 2008-2011
Sato S., Sanjo H., Takeda K., Ninomiya-Tsuji J., Yamamoto M., Kawai T., et al. Essential function for the kinase TAK1 in innate and adaptive immune responses. Nat Immunol 6 11 (2005) 1087-1095
Shim J.H., Xiao C., Paschal A.E., Bailey S.T., Rao P., Hayden M.S., et al. TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev 19 22 (2005) 2668-2681
Vallabhapurapu S., and Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27 (2009) 693-733
Dejardin E. The alternative NF-kappaB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochem Pharmacol 72 9 (2006) 1161-1179
Vallabhapurapu S., Matsuzawa A., Zhang W., Tseng P.H., Keats J.J., Wang H., et al. Non-redundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nat Immunol 9 12 (2008) 1364-1370
Liao G.X., Zhang M.Y., Harhaj E.W., and Sun S.C. Regulation of the NF-kappa B-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem 279 25 (2004) 26243-26250
Claudio E., Brown K., Park S., Wang H., and Siebenlist U. BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells. Nat Immunol 3 10 (2002) 958-965
Coope H.J., Atkinson P.G., Huhse B., Belich M., Janzen J., Holman M.J., et al. CD40 regulates the processing of NF-kappaB2 p100 to p52. EMBO J 21 20 (2002) 5375-5385
Dejardin E., Droin N.M., Delhase M., Haas E., Cao Y., Makris C., et al. The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 17 4 (2002) 525-535
Flohr S, Pyrazoloisoquinoline derivatives as kinase inhibitors. In: PCT Int. Appl. US 6,841,556, 2005.
Altschul S.F., Madden T.L., Schaffer A.A., Zhang J.H., Zhang Z., Miller W., et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25 17 (1997) 3389-3402
Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H., et al. The protein data bank. Nucleic Acids Res 28 1 (2000) 235-242
Lambert C., Leonard N., De Bolle X., and Depiereux E. ESyPred3D: prediction of proteins 3D-structures. Bioinformatics 18 9 (2002) 1250-1256
Laskowski R.A. PDBsum: summaries and analyses of PDB structures. Nucleic Acids Res 29 1 (2001) 221-222
Tripos I, SYBYL. 1699 South Hanley Rd., St. Louis, Missouri, 63144, USA.
Brown K., Vial S.C., Dedi N., Long J.M., Dunster N.J., and Cheetham G.M. Structural basis for the interaction of TAK1 kinase with its activating protein TAB1. J Mol Biol 354 5 (2005) 1013-1020
Lei M., Robinson M.A., and Harrison S.C. The active conformation of the PAK1 kinase domain. Structure 13 5 (2005) 769-778
Sali A., and Blundell T.L. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234 3 (1993) 779-815
Ghose A.K., Herbertz T., Pippin D.A., Salvino J.M., and Mallamo J.P. Knowledge based prediction of ligand binding modes and rational inhibitor design for kinase drug discovery. J Med Chem 51 17 (2008) 5149-5171
LCC DS, Pymol. 2008.
Ruegg U.T., and Burgess G.M. Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases. Trends Pharmacol Sci 10 6 (1989) 218-220
Jones G., Willett P., Glen R.C., Leach A.R., and Taylor R. Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267 3 (1997) 727-748
Saloutin V.I.Y.V.B., Skryabina Z.E., and Kuzueva O.G. Synthesis of fluoroalkyl-containing 2-oxyimino-1,3-dicarbonylcompounds and their reaction with hydrazine hydrate. J Fluorine Chem 84 (1997) 107
Majid T., Hopkins C.R., Pedgrift B., and Collar N. Convenient synthesis of 4-amino-3,5-disubstituted pyrazoles in one-step from the corresponding diketo oximes. Tetrahedron Lett 45 10 (2004) 2137-2139
Pictet A.G. Alfons, new method for the synthetic preparation of isoquinoline bases. Berichte der Dtsch Chemischen Gesellschaft 43 (1910) 2384-2391
Gaestel M., Kotlyarov A., and Kracht M. Targeting innate immunity protein kinase signalling in inflammation. Nat Rev Drug Discov 8 6 (2009) 480-499
Tang M., Wei X., Guo Y., Breslin P., Zhang S., Wei W., et al. TAK1 is required for the survival of hematopoietic cells and hepatocytes in mice. J Exp Med 205 7 (2008) 1611-1619
33PanQinase® Activity Assay performed by ProQinase, Freiburg, Germany.
Lanthascreen® Eu Kinase Binding Assay performed by Invitrogen Limited, Paisley, Scotland, United Kingdom.