Article ; Online: JAK inhibitors: Is specificity at all relevant?
Seminars in arthritis and rheumatism
2023 Volume 64S, Page(s) 152327
Abstract: Background: Cytokines are soluble factors that affect host defense and maintain immune homeostasis. Altered cytokine production leads to a dysfunctional immune responses and immune-related diseases. Cytokines bind to specific receptors and trigger ... ...
| Abstract | Background: Cytokines are soluble factors that affect host defense and maintain immune homeostasis. Altered cytokine production leads to a dysfunctional immune responses and immune-related diseases. Cytokines bind to specific receptors and trigger various intracellular signaling cascades and targeting cytokines and/or their receptors has been effective in treating inflammatory diseases. Objectives: Type I and II cytokine receptors activate four Janus kinases (JAKs), namely JAK1, JAK2, JAK3 and TYK2 and targeting of these enzymes resulted in the development of successful drugs now referred as JAK inhibitors or JAKinibs. Results: JAKinibs can be divided in three "generations." First-generation JAKinibs, molecules acting in an orthosteric manner, inhibit multiple JAKs and interfere with the biologic activity of many factors. With the idea of reducing side effects, second-generation JAKinibs, still orthosteric ATP competitors, have been developed with increased selectivity towards one or two JAKs. Third-generation JAKinibs have exploited our increased understanding of the structure and function of JAK domains and are allosteric inhibitors as they bind to specific residues in the pseudokinase domain. These third generation JAKInb indeed seems to possess a better safety profile. Notably, inhibition of cytokine activity in specific tissues could be more important than selective enzymatic blockade and for this reason, topical, inhaled, or as a non-absorbable JAKinibs are also being developed. Conclusions: While JAKinibs entered the clinical arena about ten years ago, our understanding of these drugs and their selectivity relative to their activity and safety is still incomplete. More research is therefore needed to achieve better usage of these class of drugs. |
|---|---|
| MeSH term(s) | Humans ; Janus Kinase Inhibitors/pharmacology ; Janus Kinase Inhibitors/therapeutic use ; Janus Kinases/metabolism ; Cytokines/metabolism ; Signal Transduction |
| Chemical Substances | Janus Kinase Inhibitors ; Janus Kinases (EC 2.7.10.2) ; Cytokines |
| Language | English |
| Publishing date | 2023-11-21 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 120247-9 |
| ISSN | 1532-866X ; 0049-0172 |
| ISSN (online) | 1532-866X |
| ISSN | 0049-0172 |
| DOI | 10.1016/j.semarthrit.2023.152327 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 790: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.