Exploring Established Hormonal Pathways: Selective Receptor Modulators (SRMs)
With our pioneering efforts to develop a selective estrogen receptor alpha agonist to treat advanced prostate cancer and with our leading selective androgen receptor modulator program (SARMs), we have established a strong scientific reputation for the discovery and development of small molecules that selectively bind to and modulate nuclear hormone receptors but may display unique and improved clinical activities – acting as agonist or antagonist – depending on the tissue type.
Although steroidal hormones (e.g., testosterone, estrogens, glucocorticoids, etc.) have been used as disease interventions for many years, their use has been limited by undesirable side effects or pharmacokinetic properties. GTx’s lead research and development programs are focused on the discovery and development of novel small molecules that selectively target established endocrine pathways – yielding therapeutics with the potential to address unmet medical needs in men and women.
Our robust drug discovery effort has produced a deep pipeline of clinical and preclinical product candidates that target a broad array of nuclear hormone receptors and have the potential to treat a variety of urologic, oncologic, musculoskeletal, endocrine and metabolic, ophthalmic and inflammatory diseases.
Nonsteroidal selective receptor modulators (SRMs) are designed to bind to a nuclear hormone receptor and stimulate or inhibit its activity, depending on the chemical structure of the SRM and the tissue type
Producing Beneficial Effects While Limiting Unwanted Side Effects: Molecular Endocrinology of Hormone Receptors and SRMs
The binding of a nonsteroidal hormone, or SRM, with its nuclear hormone receptor activates a series of tissue-specific cellular events, resulting in the regulation of important functions throughout the body, including metabolism and tissue growth, development and function. There are many different types of nuclear hormone receptors, intracellular proteins that mediate the activity of steroids, such as androgens and estrogens, glucocorticoids, vitamins A and D and many other steroidal ligands.
Pharmaceuticals that target nuclear hormone receptors have been prescribed for over 50 years. Steroids are characterized by a common four-ring molecular structure and activate hormone receptors in a less selective manner.
The absence of selectivity for testosterone, for example, may result in unwanted side effects such as:
- Potential stimulation of prostate cancer
- Aggravation of existing BPH
- Acne
- Hair growth or virilization
- Gynecomastia
A drug that can either block or stimulate the same nuclear hormone receptor under different conditions is called a selective receptor modulator. If it can block or stimulate a receptor in a tissue selective manner, it may be able to mimic the beneficial effects in one tissue and, at the same time, minimize the unwanted effects of the natural or synthetic steroidal hormones in other tissues.
With our expertise in selective hormonal therapeutics and our expanding portfolio of product candidates, we are building GTx into a company focused on bringing important new therapies to patients.