WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 100430
Description: Histrelin acetate is a nonapeptide analog of gonadotropin-releasing hormone (GnRH) with added potency. When present in the bloodstream, it acts on particular cells of the pituitary gland called gonadotropes. Histrelin stimulates these cells to release luteinizing hormone and follicle-stimulating hormone. Thus it is considered a gonadotropin-releasing hormone agonist or GnRH agonist. Histrelin is marketed by Endo Pharmaceuticals under the brand names Vantas and Supprelin LA. Histrelin is used to treat hormone-sensitive cancers of the prostate in men and uterine fibroids in women. In addition, histrelin has been proven to be highly effective in treating central precocious puberty in children. It is available as a daily intramuscular injection. Histrelin is also available in a 12-month subcutaneous implant (Vantas) for the palliative treatment of advanced prostate cancer (since 2005 in the US, and since Jan 2010 in the UK. A 12-month subcutaneous implant (Supprelin LA) for central precocious puberty (CPP) was approved on May 3, 2007 by the U.S. Food and Drug Administration. (See http://en.wikipedia.org/wiki/Histrelin.)
MedKoo Cat#: 100430
Name: Histrelin Acetate
Chemical Formula: C66H86N18O12
Exact Mass: 1322.66726
Molecular Weight: 1323.5
Elemental Analysis: C, 59.89; H, 6.55; N, 19.05; O, 14.51
Synonym: Supprelin LA.
IUPAC/Chemical Name: 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-Lseryl- L-tyrosyl-Nt-benzyl-D-histidyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide diacetate
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 1323.5 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Lewis KA, Goldyn AK, West KW, Eugster EA. A single histrelin implant is effective for 2 years for treatment of central precocious puberty. J Pediatr. 2013 Oct;163(4):1214-6. doi: 10.1016/j.jpeds.2013.05.033. Epub 2013 Jul 1. PubMed PMID: 23809043.
2: Gillis D, Karavani G, Hirsch HJ, Strich D. Time to menarche and final height after histrelin implant treatment for central precocious puberty. J Pediatr. 2013 Aug;163(2):532-6. doi: 10.1016/j.jpeds.2013.01.021. Epub 2013 Feb 26. PubMed PMID: 23485026.
3: Lewis KA, Eugster EA. Random luteinizing hormone often remains pubertal in children treated with the histrelin implant for central precocious puberty. J Pediatr. 2013 Mar;162(3):562-5. doi: 10.1016/j.jpeds.2012.08.038. Epub 2012 Oct 3. PubMed PMID: 23040793.
4: Shore N, Cookson MS, Gittelman MC. Long-term efficacy and tolerability of once-yearly histrelin acetate subcutaneous implant in patients with advanced prostate cancer. BJU Int. 2012 Jan;109(2):226-32. doi: 10.1111/j.1464-410X.2011.10370.x. Epub 2011 Aug 18. PubMed PMID: 21851539.
5: Djavan B, Schlegel P, Salomon G, Eckersberger E, Sadri H, Graefen M. Analysis of testosterone suppression in men receiving histrelin, a novel GnRH agonist for the treatment of prostate cancer. Can J Urol. 2010 Aug;17(4):5265-71. PubMed PMID: 20735905.
6: Hirsch HJ, Lahlou N, Gillis D, Strich D, Rosenberg-Hagen B, Chertin B, Farkas A, Hartman H, Spitz IM. Free alpha-subunit is the most sensitive marker of gonadotropin recovery after treatment of central precocious puberty with the histrelin implant. J Clin Endocrinol Metab. 2010 Jun;95(6):2841-4. doi: 10.1210/jc.2009-2078. Epub 2010 Mar 25. PubMed PMID: 20339028.
7: Deeks ED. Histrelin: in advanced prostate cancer. Drugs. 2010 Mar 26;70(5):623-30. doi: 10.2165/11204800-000000000-00000. Review. PubMed PMID: 20329807.
8: Ricker JM, Foody WF, Shumway NM, Shaw JC. Drug-induced liver injury caused by the histrelin (Vantus) subcutaneous implant. South Med J. 2010 Jan;103(1):84-6. doi: 10.1097/SMJ.0b013e3181c376a6. PubMed PMID: 19996852.
9: Rahhal S, Clarke WL, Kletter GB, Lee PA, Neely EK, Reiter EO, Saenger P, Shulman D, Silverman L, Eugster EA. Results of a second year of therapy with the 12-month histrelin implant for the treatment of central precocious puberty. Int J Pediatr Endocrinol. 2009;2009:812517. doi: 10.1155/2009/812517. Epub 2009 Feb 26. PubMed PMID: 19956699; PubMed Central PMCID: PMC2777002.
10: Lewis KA, Eugster EA. Experience with the once-yearly histrelin (GnRHa) subcutaneous implant in the treatment of central precocious puberty. Drug Des Devel Ther. 2009 Sep 21;3:1-5. PubMed PMID: 19920916; PubMed Central PMCID: PMC2769233.
Supprelin LA (histrelin acetate) subcutaneous implant contains a synthetic nonapeptide analog of the naturally occurring gonadotropin releasing hormone (GnRH) that possesses a greater potency than the natural sequence hormone. The chemical name of histrelin acetate is: L-Pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-N-benzyl-D-histidyl-L-leucyl-L-arginyl-L-proline Nethylamide, acetate salt. The molecular formula for histrelin acetate is C66H86N18O12 x 2 CH3COOH and its molecular weight is 1443.70 (or 1323.52 as free base). Histrelin is also chemically described as 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-Lseryl- L-tyrosyl-Nt-benzyl-D-histidyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide diacetate.
Mechanism of Action
Supprelin LA is a GnRH agonist and an inhibitor of gonadotropin secretion when given continuously. It delivers approximately 65 mcg histrelin acetate per day. Both animal and human studies indicate that following an initial stimulatory phase, chronic, subcutaneous administration of histrelin acetate desensitizes responsiveness of the pituitary gonadotropin which, in turn causes a reduction in ovarian and testicular steroidogenesis. In humans, administration of histrelin acetate results in an initial increase in circulating levels of LH and FSH, leading to a transient increase in concentration of gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in premenopausal females). However, continuous administration of histrelin acetate causes a reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes. These inhibitory effects result in decreased levels of LH and FSH.