An orally available small molecule that targets soluble TNF to deliver anti-TNF biologic-like efficacy in rheumatoid arthritis.
TNF
TNF trimer
immunogenicity
rheumatoid arthritis
small molecule
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2022
2022
Historique:
received:
06
09
2022
accepted:
21
10
2022
entrez:
5
12
2022
pubmed:
6
12
2022
medline:
6
12
2022
Statut:
epublish
Résumé
Tumor necrosis factor (TNF) is a pleiotropic cytokine belonging to a family of trimeric proteins with both proinflammatory and immunoregulatory functions. TNF is a key mediator in autoimmune diseases and during the last couple of decades several biologic drugs have delivered new therapeutic options for patients suffering from chronic autoimmune diseases such as rheumatoid arthritis and chronic inflammatory bowel disease. Attempts to design small molecule therapies directed to this cytokine have not led to approved products yet. Here we report the discovery and development of a potent small molecule inhibitor of TNF that was recently moved into phase 1 clinical trials. The molecule, SAR441566, stabilizes an asymmetrical form of the soluble TNF trimer, compromises downstream signaling and inhibits the functions of TNF
Identifiants
pubmed: 36467083
doi: 10.3389/fphar.2022.1037983
pii: 1037983
pmc: PMC9709720
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1037983Informations de copyright
Copyright © 2022 Vugler, O’Connell, Nguyen, Weitz, Leeuw, Hickford, Verbitsky, Ying, Rehberg, Carrington, Merriman, Moss, Nicholas, Stanley, Wright, Bourne, Foricher, Brookings, Horsley, Herrmann, Rao, Kohlmann and Florian.
Déclaration de conflit d'intérêts
AVu, JO’C, MAN, DW, TL, EH, AVe, XY, MR, BC, MM, AM, JMN, PS, SW, YF, DB, HH, MH, SR, MK and PF are either employees of UCB Pharma or Sanofi and may hold stock of the respective organizations. PF was employed by Sanofi-Aventis Deutschland GmbH at the time the work of the manuscript was conducted. He is now an employee of Boehringer Ingelheim Vetmedica GmbH. TM is employed by MilvuswoodConsultancy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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