Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 14l was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 14l as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 14l (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm201454n | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The genetic and observational nexus between diabetes and arthritis: a national health survey and mendelian randomization analysis.
Nutr Diabetes
December 2024
Department of International Medical, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
Background: Diabetes mellitus (DM) and arthritis are prevalent conditions worldwide. The intricate relationship between these two conditions, especially in the context of various subtypes of arthritis, remains a topic of interest.
Objective: To investigate the relationship between diabetes and arthritis, with a focus on Rheumatoid Arthritis (RA), using data from the National Health and Nutrition Examination Survey (NHANES) and Mendelian Randomization (MR) analysis.
Zymosan-Treated SKG Mice: Assessing Effects of Systemic Inflammation on the Temporomandibular Joint.
Oral Dis
December 2024
Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Objectives: The effects of systemic inflammation on the temporomandibular joint (TMJ) are poorly understood. This study aimed to establish a mouse model to study the effects of systemic inflammation on the TMJ.
Materials And Methods: SKG mice, a BALB/c strain with spontaneous onset of rheumatoid arthritis-like symptoms due to a spontaneous point mutation (W163C) in the gene encoding the SH2 domain of ZAP-70, were treated with zymosan (β-1,3-glucan).
Mobile Application-Based Care on Health Outcomes in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.
Public Health Nurs
December 2024
Department of Rheumatology and Immunology, Yunnan First People's Hospital, Kunming, Yunnan, People's Republic of China.
Background: Effective disease management is crucial for rheumatoid arthritis (RA) patients as it can significantly reduce disease-associated symptoms. Currently, the utilization of mobile applications for managing RA patients has gained widespread popularity in clinical settings. However, there is a notable absence of a comprehensive meta-analysis exploring their effectiveness specifically in the context of RA patients.
View Article and Find Full Text PDFPattern of Rheumatic Diseases in a New Rheumatology Clinic in Southwestern Nigeria: A Descriptive Study.
West Afr J Med
August 2024
Department of Medicine, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria. Email: Tel: 08063241116.
Background/objective: Rheumatic diseases (RMDs) are among the leading health burdens and causes of disability globally. Interestingly, they are on the rise due to the increasingly ageing population. Inflammatory RMDs are not left behind in the rise, especially in Africa, where they were thought to be rare as there has been increasing reportage of these diseases in recent years.
View Article and Find Full Text PDFImpact of Janus kinase inhibitors and methotrexate on interstitial lung disease in rheumatoid arthritis patients.
Front Immunol
December 2024
Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Objectives: Little is known about how various treatments impact the progression of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Here, we compared ILD progression in RA patients treated with Janus kinase inhibitors (JAKi) or biological disease-modifying anti-rheumatic drugs (bDMARDs). experiments were also performed to evaluate the potential effects of the drugs on epithelial-mesenchymal transition (EMT), a key event in pulmonary fibrosis.
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!