A5012390902- Dermatology and Skin Diseases
- Allergic Rhinitis and Sensitization
- Psoriasis: Treatment and Pathogenesis
- Asthma and respiratory diseases
- Cancer Mechanisms and Therapy
- Immune Cell Function and Interaction
- Contact Dermatitis and Allergies
- Urticaria and Related Conditions
- Immunotherapy and Immune Responses
- Mast cells and histamine
- Chemokine receptors and signaling
- Cancer Cells and Metastasis
Novartis (Switzerland)
2023-2024
Novartis Institutes for BioMedical Research
2023
Friedrich Miescher Institute
2021
The JAK kinases JAK1, JAK2, JAK3, and TYK2 play key roles in cytokine signaling. Activation of the JAK/STAT pathways is linked to many diseases involving immune system, including atopic dermatitis. As systemic inhibitor pharmacology associated with side effects, topical administration skin has been considered locally restrict site action. Several orally bioavailable inhibitors repurposed for use have recently approved or are clinical development. Here, we disclose our candidate CEE321, which...
Abstract Suitable human models for the development and characterization of topical compounds inflammatory skin diseases such as atopic dermatitis are not readily available to date. We describe here a translational model involving healthy mimicking major aspects AD its application Janus kinase inhibitors. Full thickness abdominal obtained from plastic surgery stimulated in vitro with IL4 IL13 shows molecular features AD. This is evidenced by STAT6 phosphorylation assessed immunohistochemistry...
We describe the discovery and characterization of supersoft topical JAK inhibitor 3(R), which is potent in biochemical cellular assays as well human skin models. In blood, neutral ester 3(R) rapidly hydrolyzed (t1/2 ∼ 6 min) to corresponding charged carboxylic acid 4 exhibiting >30-fold reduced permeability. Consequently, does not reach intracellular kinases inactive blood. Thus, hydrolysis by blood esterases leads rapid deactivation topically active at a rate beyond maximal hepatic clearance.