Small-molecule modulators of tumor necrosis factor signaling

Henri Chédotal; Dilip Narayanan; Katrine Povlsen; Charlotte H. Gotfredsen; Roberta Brambilla; Michael Gajhede; Anders Bach; Mads H. Clausen

doi:10.1016/j.drudis.2023.103575

Small-molecule modulators of tumor necrosis factor signaling

Henri Chédotal, Dilip Narayanan, Katrine Povlsen, Charlotte H. Gotfredsen, Roberta Brambilla, Michael Gajhede, Anders Bach^*, Mads H. Clausen

^*Corresponding author for this work

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Abstract

Tumor necrosis factor (TNF) is a pleiotropic cytokine with a major role in immune system homeostasis and is involved in many inflammatory and autoimmune diseases, such as rheumatoid arthritis (RA), psoriasis, Alzheimer's disease (AD), and multiple sclerosis (MS). Thus, TNF and its receptors, TNFR1 and TNFR2, are relevant pharmacological targets. Biologics have been developed to block TNF-dependent signaling cascades, but they display serious side effects, and their pharmacological effectiveness decreases over time because of their immunogenicity. In this review, we present recent discoveries in small molecules targeting TNF and its receptors and discuss alternative strategies for modulating TNF signaling.

Original language	English
Article number	103575
Journal	Drug Discovery Today
Volume	28
Issue number	6
Number of pages	9
ISSN	1359-6446
DOIs	https://doi.org/10.1016/j.drudis.2023.103575
Publication status	Published - 2023

Keywords

Inflammatory diseases
Small molecules
Tumor necrosis factor
Tumor necrosis factor receptors

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10.1016/j.drudis.2023.103575

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title = "Small-molecule modulators of tumor necrosis factor signaling",

abstract = "Tumor necrosis factor (TNF) is a pleiotropic cytokine with a major role in immune system homeostasis and is involved in many inflammatory and autoimmune diseases, such as rheumatoid arthritis (RA), psoriasis, Alzheimer's disease (AD), and multiple sclerosis (MS). Thus, TNF and its receptors, TNFR1 and TNFR2, are relevant pharmacological targets. Biologics have been developed to block TNF-dependent signaling cascades, but they display serious side effects, and their pharmacological effectiveness decreases over time because of their immunogenicity. In this review, we present recent discoveries in small molecules targeting TNF and its receptors and discuss alternative strategies for modulating TNF signaling.",

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AU - Chédotal, Henri

AU - Narayanan, Dilip

AU - Povlsen, Katrine

AU - Gotfredsen, Charlotte H.

AU - Brambilla, Roberta

AU - Gajhede, Michael

AU - Bach, Anders

AU - Clausen, Mads H.

PY - 2023

Y1 - 2023

N2 - Tumor necrosis factor (TNF) is a pleiotropic cytokine with a major role in immune system homeostasis and is involved in many inflammatory and autoimmune diseases, such as rheumatoid arthritis (RA), psoriasis, Alzheimer's disease (AD), and multiple sclerosis (MS). Thus, TNF and its receptors, TNFR1 and TNFR2, are relevant pharmacological targets. Biologics have been developed to block TNF-dependent signaling cascades, but they display serious side effects, and their pharmacological effectiveness decreases over time because of their immunogenicity. In this review, we present recent discoveries in small molecules targeting TNF and its receptors and discuss alternative strategies for modulating TNF signaling.

AB - Tumor necrosis factor (TNF) is a pleiotropic cytokine with a major role in immune system homeostasis and is involved in many inflammatory and autoimmune diseases, such as rheumatoid arthritis (RA), psoriasis, Alzheimer's disease (AD), and multiple sclerosis (MS). Thus, TNF and its receptors, TNFR1 and TNFR2, are relevant pharmacological targets. Biologics have been developed to block TNF-dependent signaling cascades, but they display serious side effects, and their pharmacological effectiveness decreases over time because of their immunogenicity. In this review, we present recent discoveries in small molecules targeting TNF and its receptors and discuss alternative strategies for modulating TNF signaling.

KW - Inflammatory diseases

KW - Small molecules

KW - Tumor necrosis factor

KW - Tumor necrosis factor receptors

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DO - 10.1016/j.drudis.2023.103575

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VL - 28

JO - Drug Discovery Today

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Small-molecule modulators of tumor necrosis factor signaling

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