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 and full antagonists 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.
Gonadotropin-releasing hormone antagonists are a class of medications that antagonize the gonadotropin-releasing hormone receptor and thus the action of gonadotropin-releasing hormone (GnRH). They are used in the treatment of prostate cancer, endometriosis, uterine fibroids, female infertility in assisted reproduction, and for other indications.
Dydrogesterone, sold under the brand name Duphaston & Dydroboon among others, is a progestin medication which is used for a variety of indications, including threatened or recurrent miscarriage during pregnancy, dysfunctional bleeding, infertility due to luteal insufficiency, dysmenorrhea, endometriosis, secondary amenorrhea, irregular cycles, premenstrual syndrome, and as a component of menopausal hormone therapy. It is taken by mouth.
Asoprisnil is a synthetic, steroidal selective progesterone receptor modulator that was under development by Schering and TAP Pharmaceutical Products for the treatment of uterine fibroids. In 2005, phase III clinical trials were discontinued due to endometrial changes in patients.
Telapristone (INN), as telapristone acetate, is a synthetic, steroidal selective progesterone receptor modulator (SPRM) related to mifepristone which is under development by Repros Therapeutics for the treatment of breast cancer, endometriosis, and uterine fibroids. It was originally developed by the National Institutes of Health (NIH), and, as of 2017, is in phase II clinical trials for the aforementioned indications. In addition to its activity as an SPRM, the drug also has some antiglucocorticoid activity.
Dienogest, sold under the brand name Visanne among others, is a progestin medication which is used in birth control pills and in the treatment of endometriosis. It is also used in menopausal hormone therapy and to treat heavy periods. Dienogest is available both alone and in combination with estrogens. It is taken by mouth.
Afimoxifene, also known as 4-hydroxytamoxifen (4-OHT) and by its tentative brand name TamoGel, is a selective estrogen receptor modulator (SERM) of the triphenylethylene group and an active metabolite of tamoxifen. The drug is under development under the tentative brand name TamoGel as a topical gel for the treatment of hyperplasia of the breast. It has completed a phase II clinical trial for cyclical mastalgia, but further studies are required before afimoxifene can be approved for this indication and marketed.
Trimegestone, sold under the brand names Ondeva and Totelle among others, is a progestin medication which is used in menopausal hormone therapy and in the prevention of postmenopausal osteoporosis. It was also under development for use in birth control pills to prevent pregnancy, but ultimately was not marketed for this purpose. The medication is available alone or in combination with an estrogen. It is taken by mouth.
Acolbifene (INN) is a nonsteroidal selective estrogen receptor modulator (SERM) which, as of 2015, is in phase III clinical trials for the treatment of breast cancer.
Isopregnanolone, also known as isoallopregnanolone and epiallopregnanolone, as well as sepranolone (INN), and as 3β-hydroxy-5α-pregnan-20-one or 3β,5α-tetrahydroprogesterone (3β,5α-THP), is an endogenous neurosteroid and a natural 3β-epimer of allopregnanolone. It has been reported to act as a subunit-selective negative allosteric modulator of the GABAA receptor, and antagonizes in animals and humans some but not all of the GABAA receptor-mediated effects of allopregnanolone, such as anesthesia, sedation, and reduced saccadic eye movements, but not learning impairment. Isopregnanolone has no hormonal effects and appears to have no effect on the GABAA receptor by itself; it selectively antagonizes allopregnanolone and does not affect the effects of other types of GABAA receptor positive allosteric modulators such as benzodiazepines or barbiturates.
Elagolix, sold under the brand name Orilissa, is a gonadotropin-releasing hormone antagonist medication which is used in the treatment of pain associated with endometriosis in women. It is also under development for the treatment of uterine fibroids and heavy menstrual bleeding in women. The medication was under investigation for the treatment of prostate cancer and enlarged prostate in men as well, but development for these conditions was discontinued. Elagolix is taken by mouth once or twice per day. It can be taken for up to 6 to 24 months, depending on the dosage.
Relugolix, sold under the brand names Orgovyx and Relumina and as one component of Myfembree, is a gonadotropin-releasing hormone antagonist medication which is used in the treatment of prostate cancer in men and uterine fibroids in women. It is also under development for use in the treatment of endometriosis. It is taken by mouth once per day.
Endoxifen, also known as 4-hydroxy-N-desmethyltamoxifen, is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group as well as a protein kinase C (PKC) inhibitor. It is under development for the treatment of estrogen receptor-positive breast cancer and for the treatment of mania in bipolar disorder. It is taken by mouth.
Fezolinetant (INN; former developmental code name ESN-364) is a small-molecule, orally active, selective neurokinin-3 (NK3) receptor antagonist which is under development by Ogeda (formerly Euroscreen) for the treatment of sex hormone-related disorders. As of May 2017, it has completed phase I and phase IIa clinical trials for hot flashes in postmenopausal women. Phase IIa trials in polycystic ovary syndrome patients are ongoing. In April 2017, it was announced that Ogeda would be acquired by Astellas Pharma.
Lonaprisan is a synthetic, steroidal antiprogestogen which was under development by Bayer HealthCare Pharmaceuticals for the treatment of endometriosis, dysmenorrhea, and breast cancer but was discontinued. It is a potent and highly selective silent antagonist of the progesterone receptor (PR). The drug reached phase II clinical trials prior to its discontinuation.
Asoprisnil ecamate (INN) is a synthetic, steroidal selective progesterone receptor modulator (SPRM) which was under development for the treatment of endometriosis, uterine fibroids, and menopausal symptoms but was discontinued. It is a potent and highly selective ligand of the progesterone receptor with mixed agonistic and antagonistic activity and much reduced antiglucocorticoid activity relative to mifepristone. The drug reached phase III clinical trials for the aforementioned indications prior to its discontinuation.
Linzagolix, sold under the brand name Yselty, is a medication used in the treatment of uterine fibroids. Linzagolix is a small-molecule, non-peptide, orally active gonadotropin-releasing hormone antagonist developed by Kissei Pharmaceutical and ObsEva.
Ozarelix is a peptide gonadotropin-releasing hormone antagonist which is or was under development by AEterna Zentaris Inc. and Spectrum Pharmaceuticals as a long-acting injection formulation for the treatment of prostate cancer. It has also been investigated for the treatment of endometriosis, but no development has been reported. The drug was previously under investigation for the treatment of benign prostatic hyperplasia and Alzheimer's disease as well, but development for these indications was discontinued. As of June 2015, it was in phase II clinical trials for prostate cancer. It seems to no longer be under development.
EM-5854 is a steroidal antiandrogen which was under development by Endoceutics, Inc. for the treatment of prostate cancer. It was first described in a patent in 2008, and was further characterized in 2012. EM-5854 reached phase I/II clinical trials for the treatment of prostate cancer but development was discontinued in March 2019.
