Science
Nuclear receptors are a class of proteins which
directly bind DNA and regulate gene expression in response to small molecule ligands. Ligand binding to a nuclear receptor may result in the
up-regulation or down-regulation of target genes. There are 48 known nuclear receptors in the human body. Nearly half of these nuclear
receptors are orphan receptors which have no known endogenous ligands.
Nuclear receptors have been implicated in a broad range of disease
states and many of them, including the estrogen, androgen and glucocorticoid hormone receptors, are highly successful drug targets.
Orphan nuclear receptors—those not yet exploited for drug
development—are a fruitful area for drug discovery. The receptors under investigation at Orphagen Pharmaceuticals have roles in autoimmune
disease, endocrine function, oncology, ophthalmological disease, and CNS disorders.
At Orphagen, we utilize our expertise in nuclear receptor screening to pursue a first-to-ligand strategy, seeking to be the first to identify operational ligands to selected orphan nuclear receptors. Once these ligands are obtained, we employ diverse resources, including internal research and external collaboration, to further elucidate the role of these receptors and validate their relevance in disease models.
Autoimmune Disease
Orphagen
pioneered the discovery of selective small molecule inhibitors of Th-17 cells, a novel class of T lymphocytes implicated in psoriasis, Crohn’s Disease,
rheumatoid arthritis, and multiple sclerosis. The project was partnered with Japan Tobacco in 2008.
Prostate & Adrenocortical Cancer
We
have identified potent antagonists to steroidogenic factor-1 (SF-1), a
promising target for the treatment of adrenocortical cancer, Cushing's
Disease, and castration resistant prostate cancer.
Psychiatric Disorders
Orphagen
is exploring targets that regulate the body’s endogenous day-night cycle (circadian rhythm) in the brain. These targets have major
potential for the treatment of sleep-wake and mood disorders.
Retinal Degeneration
The
pharmacology of a novel compound class discovered at Orphagen indicates potential for treatment of retinitis pigmentosa (RP) and the dry form
of age-related macular degeneration (AMD).
New Targets
Orphagen is screening additional orphan nuclear receptors for treatment of other cancers and dry AMD
.