Goserelin acetate

Description

Goserelin acetate, like leuprolide acetate, is a synthetic superagonist nonapeptide analogue of GnRH that possesses greater potency than the natural hormone. Note that it contains D-Ser(But) and NH-NHCONH2 in place of Gly6 and Gly10-NH2, respectively. That is, the C terminal modification simply has an NH substituting for the CH2 of Gly, and like the C-terminal change in leuprolide acetate, this inhibits enzymatic degradation of the peptide by the postproline carboxyamide peptidase.
Goserelin acetate is available in the form of a small, solid pellet that is administered as an SC implant for the palliative treatment of advanced, metastatic breast cancer in pre- and perimenopausal women or, similarly, as a palliative in advanced prostatic cancer. The rationale for this drug's use is, as described above, its ability as a superagonist to bring the levels of estradiol or testosterone to near castrate levels, thus slowing the progression of breast or prostate carcinoma, respectively. Additionally, goserelin acetate is approved for use in treating endometriosis for up to 6 months.

Description

Goserelin is a synthetic gonadotropin-releasing hormone (GNRH) agonist that binds to the GNRH receptor (GNRHR; K_i = 1.6 nM, in CHO cells expressing the human receptor). It binds to mouse pituitary αT3-1 cells and human placenta (K_ds = 2 and 580 nM, respectively) and increases intracellular calcium in αT3-1 cells. Goserelin induces testosterone production in vitro within 4 h in rat Leydig cells (ED₅₀ = 83 nM) but decreases testosterone plasma level in vivo in rats over a period of 2 to 24 weeks. It inhibits tumor growth in a DU145 human prostate carcinoma mouse xenograft model when administered at a dose of 100 μg per day. Formulations containing goserelin have been used in the treatment of hormone-dependent breast and prostate cancers, as well as endometriosis and uterine fibroids.

Chemical properties

White Solid

The Uses of Goserelin acetate

Anticancer

The Uses of Goserelin acetate

injectable gonadotropin releasing hormone superagonist (GnRH agonist) or luteinizing hormone antiproliferative activity in breast, prostate and endometrial cancers

The Uses of Goserelin acetate

Synthetic peptide agonist analog of LH-RH. Antineoplastic (hormonal).

General Description

Goserelin acetate is a synthetic decapaptide, which is a potent analog of LHRH (luteinizing hormone releasing hormone).

Biochem/physiol Actions

Goserelin acetate peptide results in significant inhibition of gonadotropin release and suppresses steroidogenesis in ovaries and testis. Thus, it leads to a reduction of testosterone to castration levels and estrogen to postmenopausal levels. Therefore, this peptide is used for reducing testosterone levels in patients with locally advanced prostate cancer.

Clinical Use

Goserelin acetate also is used in combination with the antiandrogen flutamide for shrinking prostate carcinoma before radiation therapy. This maximal androgen blockade combination is used when the prostate carcinoma has been staged as locally confined to the prostate gland, with one or both lobes as well as the seminal vesicles involved. The treatment should start 8 weeks before radiation treatment begins and be continued throughout the radiation therapy.
Furthermore, women who are to undergo hysterectomy for menorrhagia can benefit from previous treatment with goserelin acetate, because it is able to induce endometrial thinning. This thinning of the endometrium improves the operating environment by causing less intrauterine bleeding, increased postoperative amenorrhea, and decreased dysmenorrhea following surgery, which is why goserelin acetate is approved for inducing endometrial thinning prior to a patient undergoing a hysterectomy for heavy menstrual bleeding.