PMID- 35056105
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240405
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 15
IP  - 1
DP  - 2021 Dec 30
TI  - Jakinibs of All Trades: Inhibiting Cytokine Signaling in Immune-Mediated 
      Pathologies.
LID - 10.3390/ph15010048 [doi]
LID - 48
AB  - Over the last 25 years, inhibition of Janus kinases (JAKs) has been pursued as a 
      modality for treating various immune and inflammatory disorders. While the 
      clinical development of JAK inhibitors (jakinibs) began with the investigation of 
      their use in allogeneic transplantation, their widest successful application came 
      in autoimmune and allergic diseases. Multiple molecules have now been approved 
      for diseases ranging from rheumatoid and juvenile arthritis to ulcerative 
      colitis, atopic dermatitis, graft-versus-host-disease (GVHD) and other 
      inflammatory pathologies in 80 countries around the world. Moreover, two jakinibs 
      have also shown surprising efficacy in the treatment of hospitalized coronavirus 
      disease-19 (COVID-19) patients, indicating additional roles for jakinibs in 
      infectious diseases, cytokine storms and other hyperinflammatory syndromes. 
      Jakinibs, as a class of pharmaceutics, continue to expand in clinical 
      applications and with the development of more selective JAK-targeting and 
      organ-selective delivery. Importantly, jakinib safety and pharmacokinetics have 
      been investigated alongside clinical development, further cementing the potential 
      benefits and limits of jakinib use. This review covers jakinibs that are approved 
      or are under late phase investigation, focusing on clinical applications, 
      pharmacokinetic and safety profiles, and future opportunities and challenges.
FAU - Alexander, Madison
AU  - Alexander M
AD  - Translational Immunology Section, National Institute of Arthritis, 
      Musculoskeletal, and Skin Diseases, National Institutes of Health, 10 Center 
      Drive, Building 10 Room 10C211, Bethesda, MD 20892, USA.
FAU - Luo, Yiming
AU  - Luo Y
AD  - Vasculitis Translational Research Program, Systemic Autoimmunity Branch, National 
      Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes 
      of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
FAU - Raimondi, Giorgio
AU  - Raimondi G
AD  - Vascularized Composite Allotransplantation Laboratory, Department of Plastic and 
      Reconstructive Surgery, Johns Hopkins School of Medicine, 720 Rutland Ave., Ross 
      Research Building, Suite 755A, Baltimore, MD 21205, USA.
FAU - O'Shea, John J
AU  - O'Shea JJ
AD  - Molecular Immunology and Inflammation Branch, National Institute of Arthritis, 
      Musculoskeletal, and Skin Diseases, National Institutes of Health, 10 Center 
      Drive, Building 10 Room 13C103C, Bethesda, MD 20892, USA.
FAU - Gadina, Massimo
AU  - Gadina M
AUID- ORCID: 0000-0001-9084-6736
AD  - Translational Immunology Section, National Institute of Arthritis, 
      Musculoskeletal, and Skin Diseases, National Institutes of Health, 10 Center 
      Drive, Building 10 Room 10C211, Bethesda, MD 20892, USA.
LA  - eng
GR  - Intramural Research Program/AR/NIAMS NIH HHS/United States
GR  - W81XWH-18-1-0789/United States Army Medical Research Acquisition Activity/
PT  - Journal Article
PT  - Review
DEP - 20211230
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC8779366
OTO - NOTNLM
OT  - COVID-19
OT  - JAK
OT  - autoimmune diseases
OT  - cytokines
OT  - inflammation
COIS- John J. O'Shea, M.D., and the NIH hold patents related to therapeutic JAK 
      targeting and previously had a Collaborative Research Agreement and Development 
      Award with Pfizer. The other authors declare no financial or commercial conflicts 
      of interest.
EDAT- 2022/01/22 06:00
MHDA- 2022/01/22 06:01
PMCR- 2021/12/30
CRDT- 2022/01/21 01:13
PHST- 2021/11/29 00:00 [received]
PHST- 2021/12/14 00:00 [revised]
PHST- 2021/12/20 00:00 [accepted]
PHST- 2022/01/21 01:13 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/01/22 06:01 [medline]
PHST- 2021/12/30 00:00 [pmc-release]
AID - ph15010048 [pii]
AID - pharmaceuticals-15-00048 [pii]
AID - 10.3390/ph15010048 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2021 Dec 30;15(1):48. doi: 10.3390/ph15010048.