Molecules Targeting Inflammatory Signaling

Application

A group of small molecules for treating central and peripheral diseases associated with inflammation.

Key Benefits

• Applicable to a wide variety of central nervous system and peripheral diseases.
• Can bypass side effects of existing therapeutics targeting similar inflammatory pathways.
• High target selectivity and aqueous solubility.
• Capability to cross the blood brain barrier.
• Tested for efficacy and safety in preclinical in vivo models.

Market Summary

Neurological disorders like Alzheimer’s, epilepsy and Parkinson’s are distinct from peripheral conditions like cancer and inflammatory bowel disease, yet they share inflammation as a common feature and potential therapeutic target. With rising inflammation-associated disease burden, there is a heightened demand for drugs that address shared signaling pathways across conditions.

Technical Summary

Neuroinflammation is characterized by activation of complex signaling cascades. Prostanoid receptor subtype EP2 is an early member of pro-inflammatory pathways expressed in the brain and uterus, which targets adenylate cyclase and initiates downstream signaling when activated. EP2 is implicated in both central nervous system disorders (Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, status epilepticus) and peripheral diseases (rheumatoid arthritis, inflammatory bowel disease, endometriosis, cancer). Given EP2’s broad relevance to inflammatory disorders, Emory researchers synthesized and screened selective EP2 antagonists—finding candidate molecules that demonstrate potency, selectivity, aqueous solubility, and favorable toxicity profiles.

Development Stage

• Panel of therapeutics has been synthesized, screened for selectivity and potency, and tested in vivo in multiple mouse models.
• One molecule (TG11-77) has completed preclinical development through genotox, 7-day safety in rats, and efficacy in multiple disease models.
• Positioned for investigational new drug (IND) application.

Publication

• Ganesh, T., Jiang, J., & Dingledine, R. (2014). Development of second generation EP2 antagonists with high selectivity. European journal of medicinal chemistry, 82, 521-535.
• Varvel, N. H., Amaradhi, R., Espinosa-Garcia, C., Duddy, S., Franklin, R., Banik, A., ... & Dingledine, R. (2023). Preclinical development of an EP2 antagonist for post-seizure cognitive deficits. Neuropharmacology, 224, 109356.