The four members of the Janus family of nonreceptor tyrosine kinases play a significant role in immune function. The JAK family kinase inhibitor, tofacitinib , has been approved in the United States for use in rheumatoid arthritis (RA) patients. A number of JAK inhibitors with a variety of JAK family selectivity profiles are currently in clinical trials. Our goal was to identify inhibitors that were functionally selective for JAK1 and JAK3. Compound was prepared with the desired functional selectivity profile, but it suffered from poor absorption related to physical properties. Use of the phosphate prodrug enabled progression to a murine collagen induced arthritis (CIA) model. The demonstration of a robust efficacy in the CIA model suggests that use of phosphate prodrugs may resolve issues with progressing this chemotype for the treatment of autoimmune diseases such as RA.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421541 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.8b00508 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discriminative features of immunoglobulin G4-related disease (IgG4-RD) and associated autoimmune rheumatic diseases (ARDs) in a nationwide observational cohort: study from the Egyptian College of Rheumatology.
Clin Rheumatol
January 2025
Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Objective: The objective of this study is to present the clinical characteristics of immunoglobulin G4-related diseases (IgG4-RD) patients and describe associated overlap with autoimmune rheumatic diseases (ARDs).
Patients And Methods: This cross-sectional study included 81 patients with IgG4-RD who were recruited from 13 specialized rheumatology departments and centers across the country in collaboration with the Egyptian College of Rheumatology (ECR). Patients underwent a thorough history-taking and clinical examination.
Higher serotonin levels among patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis compared to healthy controls assessed by liquid chromatography-tandem mass spectrometry (LC-MS).
Rheumatol Int
January 2025
Department of Rheumatology and Immunology, Jagiellonian University Medical College, Jakubowskiego 2, Kraków, 30-688, Poland.
Growing evidence suggests that serotonin is an important mediator in the cross-talk between immune and bone cells, playing a role in the pathogenesis of various types of inflammatory arthritis (IA). However, the relationship between circulating serotonin and different outcomes in three most prevalent IA - rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA), remains limited and requires further investigation. This study was performed to evaluate variations in serotonin serum levels among RA, PsA, and axSpA and to explore the utility of this biochemical marker in the assessment of disease activity and health status measurements provided by the Multi-Dimensional Health Assessment Questionnaire (MDHAQ).
View Article and Find Full Text PDFPatient Characteristics, Diagnoses, and Management in a Combined Uveitis-Rheumatology Clinic.
Ophthalmol Ther
January 2025
Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA.
Introduction: Combined uveitis-rheumatology clinics (combined clinics) are a relatively recent clinical care model. Here we report the demographics, ocular and systemic disease characteristics, and medications utilized in patients seen in a combined clinic at a tertiary care hospital in the USA.
Methods: Medical records were reviewed of patients seen at the Combined Clinic at the University of Colorado Hospital between January 1, 2016 and November 1, 2023.
Similar Hepatitis B virus reactivation risk for patients with inflammatory arthritis or connective tissue diseases: a multicenter retrospective study.
Rheumatol Int
January 2025
Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece.
Introduction: Hepatitis B reactivation and administration of prophylactic antiviral treatment are considered in patients with autoimmune inflammatory rheumatic diseases (AIIRD) undergoing immunosuppressive/immunomodulatory treatment. Data are more robust for rheumatoid arthritis patients receiving bDMARDs but are limited for other AIIRD and drug categories.
Methods: Adult patients with AIIRD (inflammatory arthritis [IA] or connective tissue diseases [CTD]) and documented chronic or resolved HBV infection (defined as serum HBsAg positivity or anti-HBcAb positivity in the case of HBsAg non-detection respectively), followed-up in six rheumatology centers in Greece and Italy, were included.
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Rotman Research Institute, Toronto, ON, Canada.
Background: A growing body of research has focused on inflammation as both a potential biomarker and a risk factor for Alzheimer's disease (AD). The cytokine Interleukin-6 (IL-6) is involved in the pathogenesis of inflammatory disorders and in the physiological homeostasis of neural tissue. AD has been associated with increased IL-6 expression in brain, however, increased levels of IL-6 have also been linked to conditions such as diabetes and hypertension.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!