Journal of Medicinal Chemistry· 2026Q1
Discovery of DT-9081, a Potent and Orally Bioavailable Small Molecule Antagonist of the EP4 Receptor for the Treatment of Solid Cancers
- 1citations
- Q1SCImago
- 2026year
Short summary
DT-9081, a novel small molecule EP4 receptor antagonist, shows potent antagonism and favorable preclinical safety, making it a promising oral treatment candidate for solid cancers.
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Key points
- DT-9081 is a novel small molecule antagonist of the EP4 receptor.
- It was identified using a scaffold hopping strategy and optimized through SAR studies.
- DT-9081 demonstrates potent EP4R antagonism and favorable ADME characteristics.
- The compound has an excellent preclinical safety profile and modulates tumor immunity.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract The EP4 receptor (EP4R) has emerged as a promising target in immuno-oncology due to its role in modulating tumor immunity and inflammation. Here, we describe the discovery and preclinical development of DT-9081, a clinical candidate EP4R-antagonist that has completed a phase I monotherapy trial for the treatment of solid cancers. A scaffold hopping strategy enabled the identification of a novel chemical series with improved activity and pharmacokinetics. Structure–activity relationship (SAR) studies guided the optimization of lead compounds, culminating in the identification of DT-9081, which exhibits potent EP4R antagonism, favorable ADME characteristics, and an excellent preclinical safety profile. Comprehensive in vitro and in vivo pharmacology data further support the utility of DT-9081 in modulating tumor immunity, providing a compelling rationale for its clinical development in the treatment of solid cancers.
The authors' abstract, as published at the source. Journal of Medicinal Chemistry, 2026 · DOI ↗
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Field: Pharmacology (Medicine)
PharmacologyMedicine