title: Identification of human IKK-2 inhibitors of natural origin (Part II): in Silico prediction of IKK-2 inhibitors in natural extracts with known anti-inflammatory activity.
abstract: Human inhibitor NF-κB kinase 2 (hIKK-2) is the primary component responsible for activating NF-κB in response to various inflammatory stimuli. Thus, synthetic ATP-competitive inhibitors for hIKK-2 have been developed as anti-inflammatory compounds. We recently reported a virtual screening protocol (doi:10.1371/journal.pone.0016903) that is able to identify hIKK-2 inhibitors that are not structurally related to any known molecule that inhibits hIKK-2 and that have never been reported to have anti-inflammatory activity. In this study, a stricter version of this protocol was applied to an in-house database of 29,779 natural products annotated with their natural source. The search identified 274 molecules (isolated from 453 different natural extracts) predicted to inhibit hIKK-2. An exhaustive bibliographic search revealed that anti-inflammatory activity has been previously described for: (a) 36 out of these 453 extracts; and (b) 17 out of 30 virtual screening hits present in these 36 extracts. Only one of the remaining 13 hit molecules in these extracts shows chemical similarity with known synthetic hIKK-2 inhibitors. Therefore, it is plausible that a significant portion of the remaining 12 hit molecules are lead-hopping candidates for the development of new hIKK-2 inhibitors.
authors: Grup de Recerca en Nutrigenòmica, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Campus de Sescelades, C/Marcel·lí Domingo s/n, 43007 Tarragona, Catalonia, Spain.
authors: Esther
authors: E
authors: Sala
authors: Laura
authors: L
authors: Guasch
authors: Justyna
authors: J
authors: Iwaszkiewicz
authors: Miquel
authors: M
authors: Mulero
authors: Maria-Josepa
authors: MJ
authors: Salvadó
authors: Cinta
authors: C
authors: Bladé
authors: Meritxell
authors: M
authors: Ceballos
authors: Cristina
authors: C
authors: Valls
authors: Vincent
authors: V
authors: Zoete
authors: Aurélien
authors: A
authors: Grosdidier
authors: Santiago
authors: S
authors: Garcia-Vallvé
authors: Olivier
authors: O
authors: Michielin
authors: Gerard
authors: G
authors: Pujadas
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D057188:Workflow
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D051550:I-kappa B Kinase