ADX68692

ADX68692 is an orally active, follicle stimulating hormone receptor (FSHR) negative allosteric modulator (NAM) that has potential for the treatment of endometriosis and benign prostatic hyperplasia (BPH).

FSH is a hormone produced by the pituitary gland. It works synergistically with a second pituitary hormone, luteinizing hormone (LH), to control reproductive function. In women, FSH stimulates oogenesis as well as release of another hormone, called estradiol, during the first half of the menstrual cycle. LH triggers ovulation and production of progesterone. In men, FSH facilitates spermatogenesis while LH stimulates testosterone production.

Endometriosis is the result of abnormal tissue growth in female reproductive organs and is linked to excessive production of estradiol. It is a common disorder: The World Endometriosis Research Foundation estimates that there are approximately 100 million women worldwide who suffer from endometriosis. Datamonitor’s 2007 estimates suggest that about 7.5 million women in the United States who suffer from endometriosis symptoms. The most common symptoms include pain related both to menstruation (dysmenorrhea) and sexual intercourse (dyspareunia), chronic pelvic pain throughout the menstrual cycle, infertility, and menorrhagia. Current treatments include NSAIDs and off-label use of contraceptives and opioids.

Preclinical studies have demonstrated the ability of ADX68692 to reduce estradiol levels, suggesting that it could be tested as a treatment for endometriosis.

Benign prostatic hyperplasia, or BPH, is an enlargement of the prostate. BPH is characterized by hyperplasia of prostatic stromal and epithelial cells, resulting in the formation of large, fairly discrete nodules in the periurethral region of the prostate. When sufficiently large, the nodules compress the urethral canal to cause partial, or sometimes virtually complete, obstruction of the urethra, which interferes the normal flow of urine. It leads to symptoms of urinary hesitancy, frequent urination, dysuria (painful urination), increased risk of urinary tract infections, and urinary retention. Although prostate specific antigen levels may be elevated in these patients because of increased organ volume and inflammation due to urinary tract infections, BPH is not considered to be a premalignant lesion.

Androgens (testosterone and related hormones) are considered to play a permissive role, if not a causal role, in BPH by many experts. Although circulating androgen levels can be normal or low in BPH sufferers, a study published in 2008 in the journal of andrology "Andrologia" reported a newly discovered venous route by which testosterone reaches the prostate in extremely high concentrations, promoting the accelerated proliferation of prostate cells, leading to the gland's enlargement. In addition, recent research has implicated high estradiol levels with the increased growth of prostate cells.

In preclinical studies, ADX68692 was found to reduce testosterone production as well as prostate weight, suggesting that it could be tested for the treatment of BPH.

By offering a differentiated way to control the effects of FSH, ADX68692 may be able to address the causes difficult to treat disorders, including endometriosis and BPH, where hormones like estradiol and testosterone have been shown to play an important role. In addition to being differentiated by the fact that it is the only publicly disclosed non-steroidal FSHR antagonist, because of its allosteric mechanism, ADX68692 is further differentiated by the fact that it does not completely suppress the production of the hormones it regulates. This is a potential advantage because ADX68692 may offer a way to re-establish the balance for estrogen hormones in women and androgen hormones in men while avoiding side effects induced by total hormonal blockade (e.g. osteoporosis and loss of sexual appetite).


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