Small molecules as anti-TNF drugs

Tumor necrosis factor (TNF, TNF-α, cachectin) is a pleiotropic, proinflammatory cytokine with multiple biological effects, many of which are not yet fully understood. Although TNF was initially described as an anti-tumor agent more than three decades ago, current knowledge places it central to immun...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michelini, Flavia Mariana, Bueno, Carlos Alberto, Alche, Laura Edith, Ramirez, Javier Alberto
Publicado:	2015
Materias:	Cytokines Inflammation Protein-protein interactions TNF TNF inhibitors TNF-TNFR interaction adalimumab certolizumab pegol etanercept golimumab infliximab proteinase tumor necrosis factor tumor necrosis factor inhibitor tumor necrosis factor receptor proteinase inhibitor tumor necrosis factor alpha antiinflammatory activity Article cytokine production enzyme inhibition human hydrogen bond IC50 in vitro study intracellular signaling nonhuman protein expression protein function protein protein interaction animal antagonists and inhibitors metabolism signal transduction Animals Humans Protease Inhibitors Receptors, Tumor Necrosis Factor Signal Transduction Tumor Necrosis Factor-alpha
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v22_n25_p2920_Richmond http://hdl.handle.net/20.500.12110/paper_09298673_v22_n25_p2920_Richmond
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_09298673_v22_n25_p2920_Richmond
record_format	dspace
spelling	paper:paper_09298673_v22_n25_p2920_Richmond2023-06-08T15:52:28Z Small molecules as anti-TNF drugs Michelini, Flavia Mariana Bueno, Carlos Alberto Alche, Laura Edith Ramirez, Javier Alberto Cytokines Inflammation Protein-protein interactions TNF TNF inhibitors TNF-TNFR interaction adalimumab certolizumab pegol etanercept golimumab infliximab proteinase tumor necrosis factor tumor necrosis factor inhibitor tumor necrosis factor receptor proteinase inhibitor tumor necrosis factor alpha tumor necrosis factor receptor antiinflammatory activity Article cytokine production enzyme inhibition human hydrogen bond IC50 in vitro study intracellular signaling nonhuman protein expression protein function protein protein interaction animal antagonists and inhibitors metabolism signal transduction Animals Humans Protease Inhibitors Receptors, Tumor Necrosis Factor Signal Transduction Tumor Necrosis Factor-alpha Tumor necrosis factor (TNF, TNF-α, cachectin) is a pleiotropic, proinflammatory cytokine with multiple biological effects, many of which are not yet fully understood. Although TNF was initially described as an anti-tumor agent more than three decades ago, current knowledge places it central to immune system homeostasis. TNF plays a critical role in host defense against infection, as well as an inhibitory role in autoimmune disease. However, TNF overproduction generates deleterious effects by inducing the transcription of genes involved in acute and chronic inflammatory responses including asthma, rheumatoid arthritis, Crohńs disease, and psoriasis. Direct inhibition of TNF by biologics, such as monoclonal antibodies and circulating TNF receptor constructs, has produced effective treatments for these disorders and validated the inhibition of this proinflammatory cytokine as an effective therapy. Unfortunately, these biological therapies suffer from several drawbacks, including high cost and the induction of autoantibody production. Thus, the development of small molecules able to modulate TNF production or signaling pathways remains a central challenge in Medicinal Chemistry. Considerable efforts have been made over the past two decades to develop such inhibitors, which could potentially be administered orally and would presumably be cheaper. This review is focused on the recent development of compounds that modulate the activity of this cytokine by acting at different levels, such as TNF expression, processing, binding to its receptors and direct inhibition. These approaches will be compared and discussed. © 2015 Bentham Science Publishers. Fil:Michelini, F.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bueno, C.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Alché, L.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ramírez, J.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v22_n25_p2920_Richmond http://hdl.handle.net/20.500.12110/paper_09298673_v22_n25_p2920_Richmond
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Cytokines Inflammation Protein-protein interactions TNF TNF inhibitors TNF-TNFR interaction adalimumab certolizumab pegol etanercept golimumab infliximab proteinase tumor necrosis factor tumor necrosis factor inhibitor tumor necrosis factor receptor proteinase inhibitor tumor necrosis factor alpha tumor necrosis factor receptor antiinflammatory activity Article cytokine production enzyme inhibition human hydrogen bond IC50 in vitro study intracellular signaling nonhuman protein expression protein function protein protein interaction animal antagonists and inhibitors metabolism signal transduction Animals Humans Protease Inhibitors Receptors, Tumor Necrosis Factor Signal Transduction Tumor Necrosis Factor-alpha
spellingShingle	Cytokines Inflammation Protein-protein interactions TNF TNF inhibitors TNF-TNFR interaction adalimumab certolizumab pegol etanercept golimumab infliximab proteinase tumor necrosis factor tumor necrosis factor inhibitor tumor necrosis factor receptor proteinase inhibitor tumor necrosis factor alpha tumor necrosis factor receptor antiinflammatory activity Article cytokine production enzyme inhibition human hydrogen bond IC50 in vitro study intracellular signaling nonhuman protein expression protein function protein protein interaction animal antagonists and inhibitors metabolism signal transduction Animals Humans Protease Inhibitors Receptors, Tumor Necrosis Factor Signal Transduction Tumor Necrosis Factor-alpha Michelini, Flavia Mariana Bueno, Carlos Alberto Alche, Laura Edith Ramirez, Javier Alberto Small molecules as anti-TNF drugs
topic_facet	Cytokines Inflammation Protein-protein interactions TNF TNF inhibitors TNF-TNFR interaction adalimumab certolizumab pegol etanercept golimumab infliximab proteinase tumor necrosis factor tumor necrosis factor inhibitor tumor necrosis factor receptor proteinase inhibitor tumor necrosis factor alpha tumor necrosis factor receptor antiinflammatory activity Article cytokine production enzyme inhibition human hydrogen bond IC50 in vitro study intracellular signaling nonhuman protein expression protein function protein protein interaction animal antagonists and inhibitors metabolism signal transduction Animals Humans Protease Inhibitors Receptors, Tumor Necrosis Factor Signal Transduction Tumor Necrosis Factor-alpha
description	Tumor necrosis factor (TNF, TNF-α, cachectin) is a pleiotropic, proinflammatory cytokine with multiple biological effects, many of which are not yet fully understood. Although TNF was initially described as an anti-tumor agent more than three decades ago, current knowledge places it central to immune system homeostasis. TNF plays a critical role in host defense against infection, as well as an inhibitory role in autoimmune disease. However, TNF overproduction generates deleterious effects by inducing the transcription of genes involved in acute and chronic inflammatory responses including asthma, rheumatoid arthritis, Crohńs disease, and psoriasis. Direct inhibition of TNF by biologics, such as monoclonal antibodies and circulating TNF receptor constructs, has produced effective treatments for these disorders and validated the inhibition of this proinflammatory cytokine as an effective therapy. Unfortunately, these biological therapies suffer from several drawbacks, including high cost and the induction of autoantibody production. Thus, the development of small molecules able to modulate TNF production or signaling pathways remains a central challenge in Medicinal Chemistry. Considerable efforts have been made over the past two decades to develop such inhibitors, which could potentially be administered orally and would presumably be cheaper. This review is focused on the recent development of compounds that modulate the activity of this cytokine by acting at different levels, such as TNF expression, processing, binding to its receptors and direct inhibition. These approaches will be compared and discussed. © 2015 Bentham Science Publishers.
author	Michelini, Flavia Mariana Bueno, Carlos Alberto Alche, Laura Edith Ramirez, Javier Alberto
author_facet	Michelini, Flavia Mariana Bueno, Carlos Alberto Alche, Laura Edith Ramirez, Javier Alberto
author_sort	Michelini, Flavia Mariana
title	Small molecules as anti-TNF drugs
title_short	Small molecules as anti-TNF drugs
title_full	Small molecules as anti-TNF drugs
title_fullStr	Small molecules as anti-TNF drugs
title_full_unstemmed	Small molecules as anti-TNF drugs
title_sort	small molecules as anti-tnf drugs
publishDate	2015
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v22_n25_p2920_Richmond http://hdl.handle.net/20.500.12110/paper_09298673_v22_n25_p2920_Richmond
work_keys_str_mv	AT micheliniflaviamariana smallmoleculesasantitnfdrugs AT buenocarlosalberto smallmoleculesasantitnfdrugs AT alchelauraedith smallmoleculesasantitnfdrugs AT ramirezjavieralberto smallmoleculesasantitnfdrugs
_version_	1768546730066837504

Small molecules as anti-TNF drugs

Ejemplares similares