Small molecule targeting of the STAT5/6 Src homology 2 (SH2) domains to inhibit allergic airway disease.

ABSTRACT: Asthma is a chronic inflammatory disease of the lungs and airways and one of the most burdensome of all chronic maladies. Previous studies have established that expression of experimental and human asthma requires the IL-4/IL-13/IL-4 receptor α (IL-4Rα) signaling pathway, which activates the transcription factor STAT6. However, no small molecules targeting this important pathway are currently in clinical development. To this end, using a preclinical asthma model, we sought to develop and test a small-molecule inhibitor of the Src homology 2 domains in mouse and human STAT6. We previously developed multiple peptidomimetic compounds on the basis of blocking the docking site of STAT6 to IL-4Rα and phosphorylation of Tyr⁶⁴¹ in STAT6. Here, we expanded the scope of our initial in

SUBMITTER: Knight JM 

PROVIDER: S-EPMC6028980 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature