Quadragenics
Targeting the epigenome
Mucosal inflammation is a major driver of asthma, chronic obstructive lung disease, viral induced pneumonia and inflammatory bowel disease, responsible for significant morbidity. Discoveries made by the founding members of QuadraGenics have resulted in the synthesis and proof-of-concept for the development of highly selective inhibitors of Bromodomain containing protein 4 (BRD4), key component of innate inflammation responsible for activating and sustaining inflammation.
QuadraGenics Inc leverages intellectual property of its small molecule inhibitors and validated disease target to modify the epigenome to combat mucosal inflammation and its downstream fibrotic response.
Clinical Applications
Inflammatory Bowel Disease
Asthma
Fibrosis
Asthma is a chronic lung disease associated with periodic exacerbations, triggered by viral infections or allergen exposures. A subtype of patients with asthma who suffer from frequent exacerbations progress to irreversible loss of lung function as a result of structural remodeling of the airways. There are no FDA-approved therapies available that modify this fibrosis and remodeling.
We are advancing BRD4 inhibitors as treatments for airway remodeling in asthma. The potent and specific BRD4 inhibitors developed by QuadraGenics team represent the first-in-class therapy that prevents virus and allergen-induced inflammation and remodeling.
Ulcerative Colitis (UC) is one of the two major types of inflammatory bowel disease (IBD). At least 0.4% of Europeans and North Americans live with IBD, where life expectancy is significantly reduced in patients with UC that is diagnosed in childhood or with extensive colitis.
The QuadraGenics BRD4 inhibitors block acute inflammation and remodeling offer effective treatment of active UC in patients who are refractory to anti-TNFα Abs, treatment of patients with hyperplastic polyps or colonic dysplasia to prevent the development of invasive CAC, and/or the treatment of fibrosis as a result of Crohn’s disease.
Transdifferentiation of quiescent dermal fibroblasts to secretory myofibroblasts plays a central role in wound healing and pathological scar formation. This myofibroblast transdifferentiation process involves TGFb-induced de novo synthesis of alpha smooth muscle cell actin (aSMA)+ fibers that enhance contractility as well as increased expression of extracellular matrix (ECM) proteins including collagen and fibronectin.
BRD4 plays a major role in this process. BRD4 inhibition reverses hypertrophic skin fibroblast transdifferentiation to myofibroblasts and may have therapeutic indications in hypertrophic scar and pathological organ fibrosis.
Meet the Team
Jia Zhou PhD is a Professor in Pharmacology at the University of Texas Medical Branch
Allan Brasier MD is a physician investigator at the University of Wisconsin-Madison.
Targeting epigenetic modifiers of human disease