University of Pittsburgh researchers have developed a series of compounds that demonstrate promise for treating various lung diseases.
Description
Lung structures are delicate and are easily damaged by oxidants and other disease processes. Exposure to noxious agents in inspired air increases the lungs’ vulnerability. Many lung diseases caused by tissue damage to the lungs have no effective current treatment, while clinicians struggle to mitigate symptoms and slow disease progression.
The novel compounds described here contain heteroaryl rings and two electrophilic Michael acceptors, which have been found to exhibit therapeutic properties. The Michael acceptors react readily with electron-rich compounds such as thiols and react with intracellular cysteines or other targets once inside the intended cell. These novel compounds demonstrate antioxidant and anti-inflammatory properties exerted via a mechanism distinct from that of any current pulmonary medication and have not been found to cause lung injury or extrapulmonary pathology.
Applications
· Treatment of lung diseases encompassing pulmonary fibrosis, acute lung injury, lung cancer, COPD, asthma, and pulmonary hypertension
Advantages
· Direct delivery reduces or eliminates potential adverse side effects
• Short half-life of systemic circulation minimizes exposure to other tissue, further reducing risk to other organ systems
• No extrapulmonary pathology after 30 days’ exposure with dosages 10x higher than therapeutic doses
• Invention includes methods for preparing both dry powder and liquid formulations suitable for different delivery mechanisms, as well as preparation of the compound in 99% purity
• Works via a mechanism distinct from any current pulmonary medication, indicating potential therapeutic benefits alone or in combination with other current treatments
Invention Readiness
• Water-soluble derivatives suitable for delivery by inhalation have been developed.
• In vivo efficacy of the compounds has been shown in animal models of lung diseases including pulmonary fibrosis, acute lung injury, lung cancer, COPD, asthma, and pulmonary hypertension.
IP Status
https://patents.google.com/patent/US10167265B2; https://patents.google.com/patent/US9862690B2
