our science 

first-in-class drug discovery and development at unexplored nuclear receptors

Nuclear receptors are unique among transcription factors since they have well-defined pockets that allow regulation by highly potent and selective small molecule ligands. Oral drugs based on the nuclear receptors have successfully treated breast and prostate cancer, type 2 diabetes, inflammatory disease, and they hold promise for many other indications, including NASH. 

Chemical Biology Approach

Orphagen has identified small molecule ligands to several orphan nuclear receptors. We developed high throughput screening assays against diverse compound libraries. Orthogonal assays were then implemented to confirm the direct binding of ligands to the receptors. We identified both agonist and antagonist ligands which were used to support target validation. We have used publicly available databases and RNA-sequencing technology to develop therapeutic hypotheses, illustrate target engagement, and identify potential patient populations. Our unique target validation strategy allows rapid identification of lead compounds for further development.

Orphagen’s first major strategic success was a partnership with the Pharmaceutical Division of Japan Tobacco for further development of RORγ antagonists in 2008. The partnership was the first of many development programs for oral RORγ antagonists that swept the industry including Merck, Pfizer, Amgen, J&J, Abbvie, GSK, Takeda, Sanofi-Aventis and AstraZeneca. Unfortunately, no program has moved beyond a Phase 2 clinical trial in psoriasis to date.


Ongoing First-in-class Drug Discovery Pipeline

Antagonists of Steroidogenic Factor 1 (SF-1)

Retinoid antagonists

Undisclosed targets


Recent publications on OR-449

ENDO 2022

AACR 2022 

ENDO 2021


Our Assay technology