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Goserelin

Clinical data
Trade names	Zoladex, others
Other names	D-Ser(But)Azgly-GnRH
AHFS/Drugs.com	Monograph
MedlinePlus	a601002
Routes of administration	Implant
Drug class	GnRH analogue; GnRH agonist; Antigonadotropin
ATC code	L02AE03 (WHO)
Legal status
Legal status	CA: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding	27.3%
Elimination half-life	4–5 hours
Identifiers
IUPAC name N-(21-((1H-indol-3-yl)methyl)-1,1-diamino-12-(tert-butoxymethyl)-6-(2-(2-carbamoylhydrazinecarbonyl)cyclopentanecarbonyl)-15-(4-hydroxybenzyl)-18-(hydroxymethyl)-25-(1H-imidazol-5-yl)-9-isobutyl-8,11,14,17,20,23-hexaoxo-2,7,10,13,16,19,22-heptaazapentacos-1-en-24-yl)-5-oxopyrrolidine-2-carboxamide
CAS Number	65807-02-5
PubChem CID	5311128
IUPHAR/BPS	3879
DrugBank	DB00014
ChemSpider	4470656
UNII	0F65R8P09N
KEGG	D04405
ChEBI	CHEBI:5523
ChEMBL	ChEMBL1201247
CompTox Dashboard (EPA)	DTXSID7048297
ECHA InfoCard	100.212.024
Chemical and physical data
Formula	C59H84N18O14
Molar mass	1269.433 g·mol
3D model (JSmol)	Interactive image
SMILES CC(C)C(NC(=O)(COC(C)(C)C)NC(=O)(Cc1ccc(O)cc1)NC(=O)(CO)NC(=O)(Cc1cc2ccccc12)NC(=O)(Cc1cnc1)NC(=O)1CCC(=O)N1)C(=O)N(CCCN=C(N)N)C(=O)N1CCC1C(=O)NNC(N)=O
InChI InChI=1S/C59H84N18O14/c1-31(2)22-40(49(82)68-39(12-8-20-64-57(60)61)56(89)77-21-9-13-46(77)55(88)75-76-58(62)90)69-54(87)45(29-91-59(3,4)5)74-50(83)41(23-32-14-16-35(79)17-15-32)70-53(86)44(28-78)73-51(84)42(24-33-26-65-37-11-7-6-10-36(33)37)71-52(85)43(25-34-27-63-30-66-34)72-48(81)38-18-19-47(80)67-38/h6-7,10-11,14-17,26-27,30-31,38-46,65,78-79H,8-9,12-13,18-25,28-29H2,1-5H3,(H,63,66)(H,67,80)(H,68,82)(H,69,87)(H,70,86)(H,71,85)(H,72,81)(H,73,84)(H,74,83)(H,75,88)(H4,60,61,64)(H3,62,76,90)/t38-,39-,40-,41-,42-,43-,44-,45+,46-/m0/s1 Key:BLCLNMBMMGCOAS-URPVMXJPSA-N
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Goserelin, sold under the brand name Zoladex among others, is a medication which is used to suppress production of the sex hormones (testosterone and estrogen), particularly in the treatment of breast cancer and prostate cancer. It is an injectable gonadotropin releasing hormone agonist (GnRH agonist).

Structurally, it is a decapeptide. It is the natural GnRH decapeptide with two substitutions to inhibit rapid degradation.

Goserelin stimulates the production of the sex hormones testosterone and estrogen in a non-pulsatile (non-physiological) manner. This causes the disruption of the endogenous hormonal feedback systems, resulting in the down-regulation of testosterone and estrogen production.

It was patented in 1976 and approved for medical use in 1987. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Goserelin is used to treat hormone-sensitive cancers of the breast (in pre- and peri-menopausal women) and prostate, and some benign gynaecological disorders (endometriosis, uterine fibroids and endometrial thinning). In addition, goserelin is used in assisted reproduction and in the treatment of precocious puberty. It may also be used in the treatment of male-to-female transgender people.

Side effects

Goserelin may cause bone pain, hot flashes, headache, stomach upset, depression, difficulty urinating (isolated cases), weight gain, swelling and tenderness of breasts (infrequent), decreased erections and reduced sexual desire. Bone pain can be managed symptomatically, and erectile dysfunction can be treated by vardenafil (Levitra) or other similar oral therapies, although they will not treat the reduced sexual desire. The rates of gynecomastia with goserelin have been found to range from 1 to 5%.

Short-term memory impairment has also been reported in women and may in some cases be severe, but this effect disappears gradually once treatment is discontinued.<

Pharmacology

Goserelin is a synthetic analogue of a naturally occurring gonadotropin-releasing hormone (GnRH). Bioavailability is almost complete by injection. Goserelin is poorly protein-bound and has a serum elimination half-life of two to four hours in patients with normal renal function. The half-life increases with patients with impaired renal function. There is no significant change in pharmacokinetics in subjects with liver failure. After administration, peak serum concentrations are reached in about two hours. It rapidly binds to the GnRH receptor cells in the pituitary gland thus leading to an initial increase in production of luteinizing hormone and thus leading to an initial increase in the production of corresponding sex hormones. This initial flare may be treated by co-prescribing/co-administering an androgen receptor antagonist such as bicalutamide (Casodex). Eventually, after a period of about 14–21 days, production of LH is greatly reduced due to receptor downregulation, and sex hormones are generally reduced to castrate levels.

Chemistry

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Goserelin is a GnRH analogue and decapeptide. It is provided as the acetate salt.

Society and culture

Names

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Goserelin is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and BANTooltip British Approved Name.

References

1. "Product monograph brand safety updates". Health Canada. 6 June 2024. Retrieved 8 June 2024.
2. Dictionary of Organic Compounds. CRC Press. 1996. pp. 3372–. ISBN 978-0-412-54090-5.
3. Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 136–. ISBN 978-94-011-4439-1.
4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 514. ISBN 9783527607495.
5. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
6. Dittrich R, Binder H, Cupisti S, Hoffmann I, Beckmann MW, Mueller A (December 2005). "Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist". Experimental and Clinical Endocrinology & Diabetes. 113 (10): 586–92. doi:10.1055/s-2005-865900. PMID 16320157.
7. Di Lorenzo G, Autorino R, Perdonà S, De Placido S (December 2005). "Management of gynaecomastia in patients with prostate cancer: a systematic review". The Lancet. Oncology. 6 (12): 972–979. doi:10.1016/S1470-2045(05)70464-2. PMID 16321765.
8. Newton CR, Yuzpe AA, Timmon IS, Slota MD (October 1993). Memory complaints: a side effect of continued exposure to gonadotropin-releasing hormone agonists (GnRHa). Conjoint Annual Meetings of the American Fertility Society and the Canadian Fertility and Andrology Society. Montreal, Canada.
9. Friedman AJ, Juneau-Norcross M, Rein MS (February 1993). "Adverse effects of leuprolide acetate depot treatment". Fertility and Sterility. 59 (2): 448–50. doi:10.1016/s0015-0282(16)55701-x. PMID 8425646.
10. Kotake T, Usami M, Akaza H, Koiso K, Homma Y, Kawabe K, et al. (November 1999). "Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group". Japanese Journal of Clinical Oncology. 29 (11): 562–570. doi:10.1093/jjco/29.11.562. PMID 10678560.

• Medicine

• Drugs developed by AstraZeneca
• GnRH agonists
• Decapeptides
• Feminizing hormone therapy
• World Health Organization essential medicines