DT-9081: Scaffold Hopping Delivers an Oral EP4 Antagonist That Has Cleared Phase I
- EP4 blockade is an immuno-oncology idea built on PGE2-driven immune suppression in tumors.
- Scaffold hopping gave a new chemical series with better activity and pharmacokinetics, and SAR work led to DT-9081.
- It combines potent antagonism, favorable ADME and a clean preclinical safety profile, and has completed a phase I monotherapy trial in solid cancers.
💡 Points
This paper is the full med-chem story behind a compound that already has human data, which is rarer and more useful than most 'discovery of' papers. EP4 is crowded, so the interesting part is how the new series differentiates on PK and safety against earlier antagonists. I'd read it for the scaffold-hop logic and watch whether phase I translates into combination activity with checkpoint blockade.