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A Comprehensive Overview of Globally Approved JAK Inhibitors
Janus kinase (JAK) is a family of cytoplasmic non-receptor tyrosine kinases that includes four members, namely JAK1, JAK2, JAK3, and TYK2. The JAKs transduce cytokine signaling through the JAK-STAT pathway, which regulates the transcription of several genes involved in inflammatory, immune, and canc...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146299/ https://www.ncbi.nlm.nih.gov/pubmed/35631587 http://dx.doi.org/10.3390/pharmaceutics14051001 |
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author | Shawky, Ahmed M. Almalki, Faisal A. Abdalla, Ashraf N. Abdelazeem, Ahmed H. Gouda, Ahmed M. |
author_facet | Shawky, Ahmed M. Almalki, Faisal A. Abdalla, Ashraf N. Abdelazeem, Ahmed H. Gouda, Ahmed M. |
author_sort | Shawky, Ahmed M. |
collection | PubMed |
description | Janus kinase (JAK) is a family of cytoplasmic non-receptor tyrosine kinases that includes four members, namely JAK1, JAK2, JAK3, and TYK2. The JAKs transduce cytokine signaling through the JAK-STAT pathway, which regulates the transcription of several genes involved in inflammatory, immune, and cancer conditions. Targeting the JAK family kinases with small-molecule inhibitors has proved to be effective in the treatment of different types of diseases. In the current review, eleven of the JAK inhibitors that received approval for clinical use have been discussed. These drugs are abrocitinib, baricitinib, delgocitinib, fedratinib, filgotinib, oclacitinib, pacritinib, peficitinib, ruxolitinib, tofacitinib, and upadacitinib. The aim of the current review was to provide an integrated overview of the chemical and pharmacological data of the globally approved JAK inhibitors. The synthetic routes of the eleven drugs were described. In addition, their inhibitory activities against different kinases and their pharmacological uses have also been explained. Moreover, their crystal structures with different kinases were summarized, with a primary focus on their binding modes and interactions. The proposed metabolic pathways and metabolites of these drugs were also illustrated. To sum up, the data in the current review could help in the design of new JAK inhibitors with potential therapeutic benefits in inflammatory and autoimmune diseases. |
format | Online Article Text |
id | pubmed-9146299 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91462992022-05-29 A Comprehensive Overview of Globally Approved JAK Inhibitors Shawky, Ahmed M. Almalki, Faisal A. Abdalla, Ashraf N. Abdelazeem, Ahmed H. Gouda, Ahmed M. Pharmaceutics Review Janus kinase (JAK) is a family of cytoplasmic non-receptor tyrosine kinases that includes four members, namely JAK1, JAK2, JAK3, and TYK2. The JAKs transduce cytokine signaling through the JAK-STAT pathway, which regulates the transcription of several genes involved in inflammatory, immune, and cancer conditions. Targeting the JAK family kinases with small-molecule inhibitors has proved to be effective in the treatment of different types of diseases. In the current review, eleven of the JAK inhibitors that received approval for clinical use have been discussed. These drugs are abrocitinib, baricitinib, delgocitinib, fedratinib, filgotinib, oclacitinib, pacritinib, peficitinib, ruxolitinib, tofacitinib, and upadacitinib. The aim of the current review was to provide an integrated overview of the chemical and pharmacological data of the globally approved JAK inhibitors. The synthetic routes of the eleven drugs were described. In addition, their inhibitory activities against different kinases and their pharmacological uses have also been explained. Moreover, their crystal structures with different kinases were summarized, with a primary focus on their binding modes and interactions. The proposed metabolic pathways and metabolites of these drugs were also illustrated. To sum up, the data in the current review could help in the design of new JAK inhibitors with potential therapeutic benefits in inflammatory and autoimmune diseases. MDPI 2022-05-06 /pmc/articles/PMC9146299/ /pubmed/35631587 http://dx.doi.org/10.3390/pharmaceutics14051001 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Shawky, Ahmed M. Almalki, Faisal A. Abdalla, Ashraf N. Abdelazeem, Ahmed H. Gouda, Ahmed M. A Comprehensive Overview of Globally Approved JAK Inhibitors |
title | A Comprehensive Overview of Globally Approved JAK Inhibitors |
title_full | A Comprehensive Overview of Globally Approved JAK Inhibitors |
title_fullStr | A Comprehensive Overview of Globally Approved JAK Inhibitors |
title_full_unstemmed | A Comprehensive Overview of Globally Approved JAK Inhibitors |
title_short | A Comprehensive Overview of Globally Approved JAK Inhibitors |
title_sort | comprehensive overview of globally approved jak inhibitors |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146299/ https://www.ncbi.nlm.nih.gov/pubmed/35631587 http://dx.doi.org/10.3390/pharmaceutics14051001 |
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