Pharmacological Profile Of LXT-101, A Novel GnRH Antagonist, In Treatig Prostate Cancer

Prostate cancer (Pca) is one of the most common cancers and the second leading cause of cancer deaths in males in the United States. The incidence and motility of Pca in China is much lower than that in the United States, but in recent years the increased incidence in China makes it necessary to focus on the precaution and management of Pca.Orchiectomy was the most usual management, which was based on Huggins' important findings in 1941 that about 70 percent of Pca is hormone-dependent. Yet most men would not choose surgery due to the irreversibility. Thus the majority of effort has focused on those compounds reported to have chemical castration activity. One of the early drugs used for chemical castration is diethylstilbestrol (DES), a synthetic form of estrogen. It is still used in some patients today but it can possibly cause cardiovascular side effects. Antiandrogens are the other early drugs used in hormone therapy and the possible hepatotoxicity and drug resistance restrict their application.GnRH analogs, including agonists and antagonists, are synthetic analogs of gonadotropin-releasing hormone (GnRH) and act mainly on the pituitary gland in humans. Continuous treatment with GnRH agonists produces initial stimulation (7-10 days) then suppression of hormones to castrate levels. Thus the initial surge of hormone called 'flare' makes the agonists unsuitable to patients who undergo bone pain or metastasis. GnRH antagonists are developed in the recent years which can inhibit hormone production by counteracting natural GnRH binding to the pituitary receptors. These compounds are more potent compared with other hormone therapy drugs and have fewer side effects and no 'flare' caused by the agonists. To date only three antagonists called Cetrorelix,...