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.

PubMed
Abstract

Related Concept Videos

Antiasthma Drugs: Leukotriene Modifiers01:19

Antiasthma Drugs: Leukotriene Modifiers

Leukotriene modifiers, or cysteinyl leukotriene receptor antagonists, are medications used to manage chronic asthma. These agents target specific inflammatory mediators produced during arachidonic acid metabolism, an essential process in generating inflammation in the body.
Leukotriene modifiers work through two distinct mechanisms:
338
Asthma-IV: Diagnostic and Management01:30

Asthma-IV: Diagnostic and Management

The diagnosis and management of asthma are comprehensive, encompassing clinical assessments, lung function tests, and pharmacological interventions. Here's an overview:
Clinical Assessment for Asthma:
This is the first step in diagnosing and managing asthma. It includes:
2.5K
Antiasthma Drugs: β2-Adrenoceptor Agonists01:25

Antiasthma Drugs: β2-Adrenoceptor Agonists

Bronchodilators are critical in managing asthma, a chronic respiratory condition characterized by airway constriction due to inflammation and hyper-reactivity. Specifically, bronchodilators ease this constriction by relaxing the bronchial muscles, facilitating easier breathing.
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...
290
Asthma-I: Introduction01:29

Asthma-I: Introduction

Asthma is a chronic respiratory ailment that requires careful management due to its varying symptoms and influencing factors. It is characterized by airway inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction, leading to symptoms like wheezing, shortness of breath, chest tightness, and coughing. The symptom frequency and intensity may vary considerably over time. It is also linked to immune system responses to allergens and irritants, highlighting the complex...
2.7K
Asthma: Pathogenesis and Management01:20

Asthma: Pathogenesis and Management

Asthma is a chronic pulmonary condition involving inflammation of the airways, hyper-reactivity, and reversible obstruction of the airways. This condition can significantly impact a person's quality of life, making breathing difficult and leading to distressing symptoms.
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.
433
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...
9.0K