Next-Generation 5-HT-2B Serotonin-Receptor Antagonists for Anti-Fibrotic & Cardiopulmonary Therapy
This technology includes a family of small-molecule antagonists that selectively block the 5-HT2B serotonin receptor—an upstream driver of tissue-remodeling—to address fibrotic, cardiopulmonary and related disorders. Built on a conformationally-locked “(N)-methanocarba” nucleoside scaffold, the compounds show nanomolar potency, >30–400-fold selectivity over the closely related 5-HT2C receptor, and favorable oral bioavailability in rodents. In vivo mouse studies confirm functional antagonism without central nervous system side-effects, while ADMET profiling indicates metabolic stability and no hERG liability. The result is a drug-like, patent-protected platform ready for lead optimization or IND-enabling studies in lung, liver and cardiac fibrosis, pulmonary arterial hypertension, and other high-value indications.
- Disease-modifying treatment for systemic, pulmonary and hepatic fibrosis (e.g., idiopathic pulmonary fibrosis, NASH, systemic sclerosis).
- Oral or inhaled therapy for pulmonary arterial hypertension and serotonin-mediated valvular heart disease.
- Adjunct management of chronic neuropathic pain, cancer-associated cachexia and autoimmune inflammation where 5-HT-2B signaling is implicated.
- First-in-class selectivity: nanomolar 5-HT2B blockade with minimal activity at 5-HT-2A/C, GPCR off-targets or ion channels, reducing risk of valvulopathy and CNS effects.
- Drug-friendly chemistry: orally bioavailable, chemically stable small molecules amenable to cost-efficient tablet or inhaled formulations.
- Broad disease leverage: single mechanism addresses multiple fibrosis-driven pathologies—enabling portfolio or companion-therapy strategies.