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Irreversible S1PR2 Antagonists for the Treatment of Inflammation and Fibrosis
Weill Cornell Medicine
Small molecule
Immunology, Oncology, Ophthalmology
Hit To Lead or Lead Optimization
• The Technology: Lead compounds with demonstrated efficacy in the mouse bile duct ligation model
• Irreversible S1PR2 antagonists TDI-6142 and TDI- 6408 were developed based on CYM-5520 following extensive SAR studies
• TDI-6408 is a functional S1PR2 antagonist that binds irreversibly, leading to receptor endocytosis and thus overcomes the challenge of outcompeting the high concentration of circulating S1P ligand
• PoC Data: TDI-6408 dramatically increased survival (73% of animals) compared to vehicle control (27%) in the mouse bile duct ligation model
• TDI-6408 did not exhibit useful activity in the carbon tetrachloride (CCl4) fibrosis model, suggesting additional fibrosis models should be explored
• Safety: No significant interactions in broad screen of receptors, enzymes, hormones, and ion channels
Timothy Hla, Irina Jilishitz
PCT-US2019-021482 (2019.03.08)
Patent Family: PCT, US, EP
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