Related Experiment Video

Updated: Jun 24, 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

1.1K

Revisiting Structure-activity Relationships: Unleashing the potential of selective Janus kinase 1 inhibitors

Mengyi Shan1, Xuan Zhao1, Peng Sun1

  • 1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China.

Bioorganic Chemistry
|June 4, 2024
PubMed

Insights

This review highlights Janus kinase 1 (JAK1) inhibitors for treating inflammatory diseases. It examines the structure-activity relationships and druggability of potent JAK1 compounds, offering strategies to overcome clinical application challenges.

Area of Science:

  • Medicinal Chemistry
  • Immunology
  • Pharmacology

Background:

  • Janus kinases (JAKs) are non-receptor tyrosine kinases crucial for cell signaling, immune responses, and disease pathogenesis.
  • JAK1 is a key target for modulating inflammatory and immune functions, with approved drugs used in conditions like rheumatoid arthritis and atopic dermatitis.

Purpose of the Study:

  • To review current JAK1 inhibitors in the market and clinical trials.
  • To analyze the structure-activity relationships (SAR) and selectivity of highly potent JAK1 compounds (IC50 ≤ 0.1 nM).
  • To discuss the druggability of approved JAK1 drugs and potent compounds, alongside clinical application challenges and solutions.

Main Methods:

  • Literature review of approved JAK1 inhibitors and compounds in clinical trials.
  • Analysis of structural data for high-activity JAK1 inhibitors.
  • Evaluation of SAR, selectivity, and druggability profiles.

Main Results:

  • Identification and structural analysis of highly active JAK1 inhibitors.
  • Detailed examination of SAR and selectivity for potent compounds.
  • Assessment of druggability and clinical challenges associated with JAK1 inhibitors.

Conclusions:

  • JAK1 inhibitors represent a significant therapeutic strategy for inflammatory and immune-mediated diseases.
  • Understanding SAR and druggability is crucial for developing effective and safe JAK1-targeted therapies.
  • Addressing clinical application challenges will further optimize the use of JAK1 inhibitors in patient care.
Keywords:
DruggabilityJanus kinasesSelectivityStructure-activity Relationship

More Related Videos

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

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

7.9K
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

9.2K

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...
8.8K
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...
699
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.4K
Adrenergic Agonists: Chemistry and Structure-Activity Relationship01:16

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
2.9K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.4K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K