JAK inhibitors in immune-mediated rheumatic diseases: From a molecular perspective to clinical studies

Sperti, Michela; Malavolta, Marta; Ciniero, Gloria; Borrelli, Simone; Cavaglià, Marco; Muscat, Stefano; Tuszyński, Jack A.; Afeltra, Antonella; Margiotta, Domenico Paolo Emanuele; Navarini, Luca

doi:10.1016/j.jmgm.2020.107789

Cited by 3 publications

(2 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FLSs and the crucial elements produced from FLSs played important positions in inflammatory infiltration, synovial hyperplasia, and joint destruction in the onset and development of RA. , Recently, considerable attention has been made to the knowledge of pathogenesis of RA . Therefore, subsequent investigation-addressed elucidation of the mechanisms underlying CE remedy for RA was employed.…”

Section: Discussionmentioning

confidence: 99%

“…56,57 Recently, considerable attention has been made to the knowledge of pathogenesis of RA. 58 Therefore, subsequent investigation-addressed elucidation of the mechanisms underlying CE remedy for RA was employed. Jauns kinase signal transducers and activators involving various cytokines have been proven to be essential for autoimmune and other immunodeficiency syndromes, which were key factors and core hub in the progression of RA 59 and the most important drug development pathway for the treatment of RA.…”

Section: ■ Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation

Zhang

Shen

Zhao³

et al. 2021

J. Agric. Food Chem.

View full text Add to dashboard Cite

Ginger, as a food spice, is widely applied due to its extensive effects. Cedrol (CE) found in ginger is a sesquiterpene with anti-inflammatory activity. The objective of this research is to discuss the efficacy of CE on ameliorating rheumatoid arthritis (RA). CE inhibited chronic inflammation and pain in a dose-dependent manner accompanied by rapid onset and long duration. Besides, CE treatment effectively ameliorated the paw edema volume and arthritis score with no significant effect on body weight. Organ index, T-cell and B-cell proliferation, histopathology, and immunohistochemistry demonstrated that CE had immunological enhancement and attenuated RA effects. Remarkably, inhibition of phosphorylated-JAK3 protein, thereby abating the secretion of pro-inflammatory cytokines and inflammation-related mediators, was involved in the potential mechanism of CE efficiency through forming a hydrogen bond with ARG953 and ILE955 in the JAK3 active pocket. At the same time, the pharmacokinetic results showed that the absolute bioavailability of CE at 20, 40, and 80 mg/kg was 30.30, 23.68, and 16.11%, respectively. The current results offered clues for mastering the ameliorated RA of CE and further perfected the effective substance basis on the antiinflammatory effect of ginger, which was beneficial for further applications.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation

Zhang

Shen

Zhao³

et al. 2021

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

Introduction to molecular pharmacology: basic concepts

Afzal

Kazmi

Kaur

et al. 2023

How Synthetic Drugs Work

View full text Add to dashboard Cite

Targeting TYK2 for Fighting Diseases: Recent Advance of TYK2 Inhibitors

Rao

Fang

et al. 2024

CMC

View full text Add to dashboard Cite

TYK2 (tyrosine-protein kinase 2) is a non-receptor protein kinase belonging to the JAK family and is closely associated with various diseases, such as psoriasis, inflammatory bowel disease, systemic lupus erythematosus. TYK2 activates the downstream proteins STAT1-5 by participating in the signal transduction of immune factors such as IL-12, IL-23, and IL-10, resulting in immune expression. The activity of the inhibitor TYK2 can effectively block the transduction of excessive immune signals and treat diseases. TYK2 inhibitors are divided into two types of inhibitors according to the different binding sites. One is a TYK2 inhibitor that binds to JH2 and inhibits its activity through an allosteric mechanism. The representative inhibitor is BMS-986165, developed by Bristol-Myers Squibb. The other class binds to the JH1 adenosine triphosphate (ATP) site and prevents the catalytic activity of the kinase by blocking ATP and downstream phosphorylation. This paper mainly introduces the protein structure, signaling pathway, synthesis, structure-activity relationship and clinical research of TYK2 inhibitors.

show abstract

JAK inhibitors in immune-mediated rheumatic diseases: From a molecular perspective to clinical studies

Cited by 3 publications

References 134 publications

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation

Introduction to molecular pharmacology: basic concepts

Targeting TYK2 for Fighting Diseases: Recent Advance of TYK2 Inhibitors

Contact Info

Product

Resources

About