A novel JAK/ROCK inhibitor, CPL409116, demonstrates potent efficacy in the mouse model of systemic lupus erythematosus.
Animals
Cells, Cultured
Disease Models, Animal
Disease Progression
Female
Janus Kinase Inhibitors
/ pharmacology
Janus Kinases
/ physiology
Lupus Erythematosus, Systemic
/ drug therapy
Mice, Transgenic
Piperidines
/ pharmacology
Pyrimidines
/ pharmacology
Treatment Outcome
rho-Associated Kinases
/ antagonists & inhibitors
JAK1
JAK3
Lupus
Nephritis
ROCK
Journal
Journal of pharmacological sciences
ISSN: 1347-8648
Titre abrégé: J Pharmacol Sci
Pays: Japan
ID NLM: 101167001
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
13
10
2020
revised:
20
01
2021
accepted:
01
02
2021
entrez:
13
3
2021
pubmed:
14
3
2021
medline:
11
9
2021
Statut:
ppublish
Résumé
Systemic lupus erythematosus is a chronic inflammatory disease, in which treatment is still limited due to suboptimal efficacy and toxicities associated with the available therapies. JAK kinases are well known to play an important role in systemic lupus erythematous. There is growing evidence that ROCK kinases are also important in disease development. In this paper, we present the results of the development of CPL409116, a dual JAK and ROCK inhibitor. The studies we performed demonstrate that this molecule is an effective JAK and ROCK inhibitor which efficiently blocks disease progression in NZBWF1/J mouse models of systemic lupus erythematous.
Identifiants
pubmed: 33712286
pii: S1347-8613(21)00013-X
doi: 10.1016/j.jphs.2021.02.002
pii:
doi:
Substances chimiques
Janus Kinase Inhibitors
0
Piperidines
0
Pyrimidines
0
tofacitinib
87LA6FU830
Janus Kinases
EC 2.7.10.2
rho-Associated Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
340-348Informations de copyright
Copyright © 2021 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest All authors of this paper were employees of Celon Pharma S.A. MW and JSP owns stocks of Celon Pharma S.A.