A selective progesterone receptor modulator (SPRM) is an agent that acts on the progesterone receptor (PR), the biological target of progestogens like progesterone. A characteristic that distinguishes such substances from full receptor agonists (e.g., progesterone, progestins) and full antagonists (e.g., aglepristone) is that their action differs in different tissues, i.e. agonist in some tissues while antagonist in others. This mixed profile of action leads to stimulation or inhibition in tissue-specific manner, which further raises the possibility of dissociating undesirable adverse effects from the development of synthetic PR-modulator drug candidates.
Ever since the discovery of the progesterone hormone in the mid-1930s. and especially after the discovery of its receptor in 1970 there has been a significant interest in developing an antagonistic agent for therapeutic use. Various progesterone analogs, known as progestins, were synthesized and in 1981 the first progesterone receptor antagonist was introduced by the name RU 38486 (RU 486, mifepristone). However, the clinical limitation of mifepristone due to its relatively high binding affinity for glucocorticoid receptor compared to the progesterone receptor has sparked the demand for more selective progesterone antagonist to minimize risk of adverse effects. As a contribution, so-called Selective Progesterone Receptor Modulators (SPRMs) have been developed. They have been described as agents with mixed antagonistic and agonistic effects on progesterone receptors in a tissue specific manner, while minimizing interactions with other steroidal receptors. Opposed to progesterone antagonists, the mixed agonist-antagonist SPRM, due to their intrinsic progesterone agonistic activity, have an absent or only a minimal effect on pregnancy termination and are thus ideal for treating gynecological conditions without eliminating the potential of pregnancy. Both steroidal and non steroidal SPRMs have been described and the most notable examples are asoprisnil, which failed phase 3 clinical trial in 2008, and ulipristal acetate, the first SPRM on the market (2009 in Europe).
This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.
This course will convey the concepts and experimental techniques for studying the signal transduction mediated by receptors across biological membranes.
This course introduces the student to the fudamentals of pharmacology, pharmacokinetics and drug-receptor interactions. It discusses also pharmacogenetics and chronopharmacology, to exemplify the chal
Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Lesions can be found on ovaries, fallopian tubes, tissue around the uterus and ovaries (peritoneum), intestines, bladder, and diaphragm; it may also occur in other parts of the body. Some symptoms include pelvic pain, heavy periods, pain with bowel movements, painful urination, pain during sexual intercourse and infertility.
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists and antagonists (that is, full agonists and silent antagonists) is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.
G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often l ...
2024
,
The presurgical window of opportunity trial (WOT) MIPRA provides evidence that neoadjuvant treatment with the prog-esterone receptor (PR) antagonist mifepristone (RU486) may benefit patients with estrogen receptor-positive (ER+) breast cancer characterized ...
AMER ASSOC CANCER RESEARCH2023
, , ,
Objective. Peripheral nerve interfaces have the potential to restore sensory, motor, and visceral functions. In particular, intraneural interfaces allow targeting deep neural structures with high selectivity, even if their performance strongly depends upon ...