Related Experiment Video

Updated: Jun 6, 2026

Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway
08:15

Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway

Published on: May 10, 2024

The use of structural biology in Janus kinase targeted drug discovery

Nilda L Alicea-Velázquez1, Titus J Boggon

  • 1Department of Pharmacology, Yale University School of Medicine, 333 Cedar St., SHM B-316A, New Haven, CT 06520, USA.

Current Drug Targets
|December 4, 2010
PubMed

Insights

Janus kinases (Jak) are crucial for cell signaling. Understanding Jak kinase domain structures advances the development of targeted therapies for cancers and immune disorders.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Janus kinases (Jak) mediate essential cytokine and growth factor signaling pathways.
  • Dysregulated Jak signaling, due to mutations, is implicated in various cancers, including leukemias, and immunodeficiencies.
  • The discovery of the Jak2 V617F mutation spurred interest in Jak2-specific inhibitors.

Purpose of the Study:

  • To review recent advancements in the structural biology of the Jak kinase domain.
  • To highlight the functional insights gained from available Jak kinase domain structures.
  • To discuss the impact of structural understanding on developing Jak-targeted therapeutics.

Main Methods:

  • Review of existing literature on Janus kinase family members (Jak1, Jak2, Jak3, Tyk2).
  • Focus on structural biology of the Jak kinase domain.
  • Analysis of structure-function relationships relevant to drug development.

Main Results:

  • Over 20 public structures of Jak kinase domains are available, covering all four family members.
  • Structural data provides insights into the druggable nature of the Jak kinase domain.
  • Understanding these structures is key to designing specific tyrosine kinase inhibitors.

Conclusions:

  • Advances in structural biology have significantly enhanced our understanding of the Jak kinase family.
  • This knowledge is pivotal for the rational design of novel Jak-targeted therapeutics.
  • Targeting Jak kinases holds promise for treating hematological malignancies and immune disorders.

More Related Videos

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

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...
Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...