Academic Journal
NF-κB inducing kinase (NIK) inhibitors: Identification of new scaffolds using virtual screening
| العنوان: | NF-κB inducing kinase (NIK) inhibitors: Identification of new scaffolds using virtual screening |
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| المؤلفون: | Mortier, Jérémie, Masereel, Bernard, Remouchamps, Caroline, Ganeff, Corinne, Piette, Jacques, Frédérick, Raphaël |
| المساهمون: | UCL - SSS/LDRI - Louvain Drug Research Institute |
| المصدر: | Bioorganic & Medicinal Chemistry Letters : the tetrahedron journal for research at the interface of chemistry and biology, Vol. 20, no. 15, p. 4515-4520 (2010) |
| بيانات النشر: | Pergamon |
| سنة النشر: | 2010 |
| المجموعة: | DIAL@USL-B (Université Saint-Louis, Bruxelles) |
| مصطلحات موضوعية: | NF-κB inducing kinase, Protein serine threonine kinase inhibitor, Staurosporine, Unclassified drug, NF kappa B kinase, NF-kappa B kinase, Protein kinase inhibitor, Protein serine threonine kinase, Recombinant protein, Article, Competitive inhibition, NIK, Concentration (parameters), Drug structure, Enzyme inhibition, High throughput screening, IC 50, Model, Molecular docking, Molecular dynamics, Binding site, Chemistry, Virtual screening, Computer simulation, Drug antagonism, Genetics, Human, Metabolism, Rheumatoid arthritis, Arthritis |
| الوصف: | As a wide variety of pro-inflammatory cytokines are involved in the development of rheumatoid arthritis (RA), there is an urgent need for the discovery of novel therapeutic strategies. Among these, the inhibition of the NF-κB inducing kinase (NIK), a key enzyme of the NF-κB alternative pathway activation, represents a potential interesting approach. In fact, NIK is involved downstream of many tumor necrosis factor receptors (TNFR) like CD40, RANK or LTβR, implicated in the pathogenesis of RA. But, up to now, the number of reported putative NIK inhibitors is extremely limited. In this work, we report a virtual screening (VS) study combining various filters including high-throughput docking using a 3D-homology model and ranking by using different scoring functions. This work led to the identification of two molecular fragments, 4H-isoquinoline-1,3-dione (5) and 2,7-naphthydrine-1,3,6,8-tetrone (6) which inhibit NIK with an IC50 value of 51 and 90 μM, respectively. This study opens new perspectives in the field of the NF-κB alternative pathway inhibition. © 2010 Elsevier Ltd. All rights reserved. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0960-894X 1464-3405 |
| Relation: | boreal:162919; http://hdl.handle.net/2078.1/162919; urn:ISSN:0960-894X; urn:EISSN:1464-3405 |
| DOI: | 10.1016/j.bmcl.2010.06.027 |
| الاتاحة: | http://hdl.handle.net/2078.1/162919 https://doi.org/10.1016/j.bmcl.2010.06.027 |
| Rights: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.83F797F1 |
| قاعدة البيانات: | BASE |
| تدمد: | 0960894X 14643405 |
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| DOI: | 10.1016/j.bmcl.2010.06.027 |