Related Experiment Video

Updated: Sep 21, 2025

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
08:36

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Published on: April 7, 2023

1.2K

A Comprehensive Overview of Globally Approved JAK Inhibitors

Ahmed M Shawky1, Faisal A Almalki2, Ashraf N Abdalla3,4

  • 1Science and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi Arabia.

Pharmaceutics
|May 28, 2022
PubMed

Insights

This review details eleven approved Janus kinase (JAK) inhibitors, exploring their chemistry, pharmacology, and clinical uses. The findings aid in developing new JAK inhibitors for inflammatory and autoimmune diseases.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Medicinal Chemistry

Background:

  • Janus kinases (JAKs) are critical cytoplasmic tyrosine kinases regulating cytokine signaling via the JAK-STAT pathway.
  • Dysregulation of JAK-STAT signaling is implicated in inflammatory, immune, and cancer conditions.
  • Small-molecule JAK inhibitors offer therapeutic potential for various diseases.

Purpose of the Study:

  • To provide a comprehensive overview of eleven globally approved JAK inhibitors.
  • To integrate chemical, pharmacological, and structural data for these drugs.
  • To facilitate the design of novel JAK inhibitors for therapeutic applications.

Main Methods:

  • Review of chemical synthesis routes for eleven approved JAK inhibitors.
  • Analysis of inhibitory activities against various kinases and pharmacological applications.
  • Summarization of crystal structures, binding modes, and interactions with kinases.
  • Illustration of proposed metabolic pathways and metabolites.

Main Results:

  • Detailed descriptions of synthetic pathways for eleven JAK inhibitors.
  • Explanation of kinase inhibitory profiles and clinical uses.
  • Elucidation of structural interactions and binding modes.
  • Identification of metabolic pathways and key metabolites.

Conclusions:

  • The integrated data on approved JAK inhibitors can guide the development of new therapeutic agents.
  • This review highlights the potential of JAK inhibitors in treating inflammatory and autoimmune diseases.
  • Understanding JAK inhibitor mechanisms and properties is crucial for future drug design.
Keywords:
JAKbinding mode/interactionskinase inhibitory activitypharmacological usessynthesis

More Related Videos

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.0K
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

8.0K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.3K
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
271
Drug Administration and Therapy Phases: Overview01:26

Drug Administration and Therapy Phases: Overview

Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
792
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
852
Pharmacokinetics: Overview01:10

Pharmacokinetics: Overview

Pharmacokinetics is a scientific discipline that focuses on the journey of a drug within the body, encompassing four key stages: absorption, distribution, metabolism, and elimination. The first stage, absorption, involves the drug's transfer into the bloodstream. Several factors dictate the extent and speed of this process. For example, the liver often metabolizes oral drugs before they reach systemic circulation, leading to only partial absorption. In contrast, intravenous (IV)...
7.3K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
7.6K