Gα12 inhibition serves as a novel bronchodilator

Inventor (s): Reynold A. Panettieri, Jr., MD

Date Awarded: October 2021

Summary:

Asthma and chronic obstructive lung disease represent very common and costly global health threats. Airway inflammation and bronchoconstriction are the cornerstone in the pathogenesis of asthma and COPD. No one drug or mechanism of action can effectively treat either disease and thus dual therapy with two drugs need to address inflammation and bronchoconstriction. Despite remarkable progress in the development of new anti-inflammatory drugs to treat these disorders, there been a lack in progress regarding the development of novel bronchodilator therapy. In fact, no novel bronchodilator has been developed in the past 30 years. Using a novel platform for characterization of drugs effects on human airway smooth muscle, the pivotal cell regulating bronchoconstriction, we discovered that inhibitors of Gα12 can profoundly inhibit contraction of human airway smooth muscle in manner greater than industry standard, beta agonists or receptor antagonists. This proposal seeks to optimize our lead candidate molecule for bioavailability, specificity and efficacy. Ultimately, this optimization will facilitate drug development as a new bronchodilator alone as rescue therapy for acute symptoms, or in combination with anti-inflammatory agents in the management of the chronic disease.

Market Applications:

• The characterization of an inhibitor of Gα12as a novel bronchodilator in the treatment of asthma and COPD.
• Optimize target engagement and diminish off target effects for oral or inhaled therapy.
• Can be used as rescue or chronic therapy that can be combined with an anti-inflammatory agent.