HiJAKing SARS-CoV-2? The potential role of JAK inhibitors in the management of COVID-19

The development of kinase and phosphatase inhibitors as novel therapeutic agents has been stimulated by the discovery that most biological processes are controlled by the reversible phosphorylation of proteins. Most of the early results in this area were generated in oncology, at the same time as the human genome, with its 500+ kinases and 100+ phosphatases was deciphered. Because of this, we know a great deal about which processes signalling inhibitors interfere with, but little about the overall consequences. In this study, kinases will be briefly reviewed, followed by some of the early problems in developing kinase inhibitors, as biochemical reagents, and clinically active pharmaceuticals in oncology. The discussion will then switch to the potential role of kinases and phosphatases in controlling the disease process in Type II diabetes. Phosphatase inhibitors should augment insulin receptor tyrosine kinase signalling. Glycogen synthesis and glycogenolysis are phosphorylation dependent, and amenable to kinase inhibition, as are some nuclear hormone receptors, and these will be briefly discussed.

Download Full-text

Potential role of multi-targeted tyrosine kinase inhibitors in non-small-cell lung cancer

Annals of Oncology ◽

10.1093/annonc/mdm412 ◽

2007 ◽

Vol 18 ◽

pp. x32-x41 ◽

Cited By ~ 11

Author(s):

G.V. Scagliotti

Keyword(s):

Lung Cancer ◽

Tyrosine Kinase ◽

Small Cell Lung Cancer ◽

Tyrosine Kinase Inhibitors ◽

Cell Lung Cancer ◽

Potential Role ◽

Kinase Inhibitors ◽

Small Cell ◽

Small Cell Lung

Download Full-text

The potential role of Aurora kinase inhibitors in haematological malignancies

British Journal of Haematology ◽

10.1111/j.1365-2141.2011.08898.x ◽

2011 ◽

Vol 155 (5) ◽

pp. 561-579 ◽

Cited By ~ 41

Author(s):

Sherif S. Farag

Keyword(s):

Potential Role ◽

Kinase Inhibitors ◽

Aurora Kinase ◽

Haematological Malignancies ◽

Aurora Kinase Inhibitors

Download Full-text

Assessing the potential role of next generation tyrosine kinase inhibitors in the treatment of cancers with acquired kinase domain mutations

Oral Oncology ◽

10.1016/j.oraloncology.2017.09.001 ◽

2017 ◽

Vol 73 ◽

pp. 172

Author(s):

A. Thirumal Raj ◽

Shankargouda Patil ◽

R. Ranadheer ◽

R. Chandini

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Potential Role ◽

Kinase Inhibitors ◽

Kinase Domain ◽

Next Generation ◽

Kinase Domain Mutations

Download Full-text

Role of Janus Kinase Inhibitors in Therapy of Psoriasis

Journal of Clinical Medicine ◽

10.3390/jcm10194307 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4307

Author(s):

Sylwia Słuczanowska-Głąbowska ◽

Anna Ziegler-Krawczyk ◽

Kamila Szumilas ◽

Andrzej Pawlik

Keyword(s):

Side Effects ◽

First Generation ◽

Kinase Inhibitors ◽

Janus Kinase ◽

Jak Inhibitors ◽

Biologic Drugs ◽

Janus Kinases ◽

Janus Kinase Inhibitors ◽

Long Term Treatment

Janus kinases inhibitors are molecules that target Janus kinases—signal transducers and activators of transcription (JAK/STAT). They inhibit this intracellular signal pathway, blocking the gene transcription of crucial proinflammatory cytokines that play a central role in the pathogenesis of many inflammatory and autoimmune diseases, including psoriasis. This process reduces psoriatic inflammation. The JAK inhibitors are divided into two generations. The first generation of JAK inhibitors blocks two or more different Janus kinases. The second generation is more specified and blocks only one type of Janus kinase and has less side effects than the first generation. Tofacitinib, ruxolitinib and baricitinib belong to first generation JAK inhibitors and decernotinib and filgotinib belong to second group. This narrative review summarizes the role of Janus kinase inhibitors in the therapy of psoriasis. Oral JAK inhibitors show promise for efficacy and safety in the treatment of psoriasis. Studies to date do not indicate that JAK inhibitors are superior to recent biologic drugs in terms of efficacy. However, JAK inhibitors, due to their lack of increased incidence of side effects compared to other biologic drugs, can be included in the psoriasis treatment algorithm because they are orally taken. Nevertheless, further studies are needed to evaluate long-term treatment effects with these drugs.

Download Full-text