TY - JOUR
T1 - Small-molecule modulators of tumor necrosis factor signaling
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.
N1 - Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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.
U2 - 10.1016/j.drudis.2023.103575
DO - 10.1016/j.drudis.2023.103575
M3 - Review
C2 - 37003513
SN - 1359-6446
VL - 28
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 6
M1 - 103575
ER -