Related Experiment Video
Updated: Jul 16, 2025

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
Discovery of the Potent and Selective Inhaled Janus Kinase 1 Inhibitor AZD4604 and Its Preclinical Characterization
Magnus Nilsson1, Kristina Berggren1, Susanne Berglund1
1Medicinal Chemistry, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg SE-431 83, Sweden.
None:
JAK-STAT cytokines are critical in regulating immunity. Persistent activation of JAK-STAT signaling pathways by cytokines drives chronic inflammatory diseases such as asthma. Herein, we report on the discovery of a highly JAK1-selective, ATP-competitive series of inhibitors having a 1000-fold selectivity over other JAK family members and the approach used to identify compounds suitable for inhaled administration. Ultimately, compound 16 was selected as the clinical candidate, and upon dry powder inhalation, we could demonstrate a high local concentration in the lung as well as low plasma concentrations, suggesting no systemic JAK1 target engagement. Compound 16 has progressed into clinical trials. Using 16, we found JAK1 inhibition to be more efficacious than JAK3 inhibition in IL-4-driven Th2 asthma.
Related Concept Videos
Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
Asthma-IV: Diagnostic and Management
Clinical Assessment for Asthma:
This is the first step in diagnosing and managing asthma. It includes:
Antiasthma Drugs: β2-Adrenoceptor Agonists
One class of bronchodilators includes β2-adrenoceptor agonists. These agents target the β2-adrenoceptors located on bronchial smooth muscle cells. By stimulating these receptors, β2-agonists induce...
Asthma-I: Introduction
Asthma: Pathogenesis and Management
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
The JAK-STAT Signaling Pathway

