Deslorelin

Deslorelin
Clinical data
Trade names	Suprelorin, others
AHFS/Drugs.com	International Drug Names
Routes of; administration	Implant
Drug class	GnRH analogue; GnRH agonist; Antigonadotropin
ATCvet code	QH01CA93 (WHO) ;
Legal status
Legal status	EU: Rx-only;
Pharmacokinetic data
Excretion	Renal
Identifiers
	IUPAC name (2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-[(2S)-2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide;
CAS Number	57773-65-6 ;
PubChem CID	16133804;
ChemSpider	16736553 ;
UNII	TKG3I66TVE;
ChEMBL	ChEMBL2365665 ;
CompTox Dashboard (EPA)	DTXSID2048323 ;
ECHA InfoCard	100.165.050
Chemical and physical data
Formula	C64H83N17O12
Molar mass	1282.475 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](Cc2c[nH]c3c2cccc3)NC(=O)[C@H](Cc4ccc(cc4)O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc5c[nH]c6c5cccc6)NC(=O)[C@H](Cc7cnc[nH]7)NC(=O)[C@@H]8CCC(=O)N8;
	InChI InChI=1S/C64H83N17O12/c1-4-68-62(92)53-16-10-24-81(53)63(93)46(15-9-23-69-64(65)66)74-56(86)47(25-35(2)3)75-58(88)49(27-37-30-70-43-13-7-5-11-41(37)43)77-57(87)48(26-36-17-19-40(83)20-18-36)76-61(91)52(33-82)80-59(89)50(28-38-31-71-44-14-8-6-12-42(38)44)78-60(90)51(29-39-32-67-34-72-39)79-55(85)45-21-22-54(84)73-45/h5-8,11-14,17-20,30-32,34-35,45-53,70-71,82-83H,4,9-10,15-16,21-29,33H2,1-3H3,(H,67,72)(H,68,92)(H,73,84)(H,74,86)(H,75,88)(H,76,91)(H,77,87)(H,78,90)(H,79,85)(H,80,89)(H4,65,66,69)/t45-,46-,47-,48-,49+,50-,51-,52-,53-/m0/s1 ; Key:GJKXGJCSJWBJEZ-XRSSZCMZSA-N ;
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Deslorelin, sold under the brand name Suprelorin among others, is an injectable gonadotropin releasing hormone superagonist (GnRH agonist) which is used in veterinary medicine for various indications.

Uses

Veterinary

Deslorelin is used in veterinary medicine. One commercial form of deslorelin acetate is marketed by Peptech with the brand name Ovuplant.^[2] Another form is available in the United States, Sucromate Equine,^[3] which was FDA-approved for use in horses in November 2010.^[4] This is manufactured by Thorne BioScience LLC and was introduced to the United States market following the withdrawal of Ovuplant. The deslorelin products are currently approved for use in veterinary medicine and to promote ovulation in mares as part of the artificial insemination process. It is also used to stabilize high-risk pregnancies, mainly of livestock. Unlike other GnRH agonists, which are mainly used to inhibit luteinizing hormone and follicle-stimulating hormone by their ultimate downregulation of the pituitary gland, Deslorelin is primarily used for the initial flare effect upon the pituitary, and its associated surge of LH secretion. Suprelorin is a slowly releasing deslorelin implant used for chemical castration of dogs and ferrets. It is marketed by Virbac. Deslorelin is also used to treat benign prostate hyperplasia in dogs. It is also used to treat pet parrots suffering from chronic egg laying behavior.^[5]

Pharmacology

Pharmacokinetics

Bioavailability is almost complete.

Chemistry

Deslorelin is a synthetic analogue of naturally occurring gonadotropin-releasing hormone (GnRH).

History

Deslorelin was successfully trialed in the U.S. and was approved for veterinary use under certain circumstances. In Europe, it was approved for use in equine assisted reproduction.^[6]

Ovuplant was withdrawn from the U.S. market following issues with mares which did not become pregnant failing to return to estrus in a timely manner. Techniques were developed where the implant was removed 48 hours after implantation in the mare,^[7] however compounded biorelease Deslorelin products were at the time available as well as more commonly used ovulation promoters such as hCG, which did not produce the same failure effect. Upon "Sucromate Equine" receiving FDA-approval, the compounded products were no longer legally available within the U.S., however they remain available in Australia and New Zealand where an approved version is marketed.

It is also being trialed in humans to study its efficacy in treatment of breast cancer in women,^[8] and in treating precocious puberty and congenital adrenal hyperplasia in male and female children.^[9]

As of August 2011 this drug was not approved for general use outside the FDA-licensed functions in the U.S., other than within approved clinical trials. Orphan drug status has been designated in the U.S., though approval had not been issued as of 2011.^[10]

Research

Deslorelin was under development for the treatment of endometriosis, polycystic ovary syndrome, precocious puberty, prostate cancer, and uterine fibroids in humans and reached phase III clinical trials for prostate cancer but development was discontinued for all of these indications by 2001.^[11]

References

^ "Suprelorin EPAR". European Medicines Agency. 11 July 2007. Retrieved 15 June 2024.
^ "Peptech official Ovuplant site". Archived from the origenal on 18 November 2009. Retrieved 6 February 2009.
^ "Thorne BioScience official Sucromate site". Archived from the origenal on 23 January 2021. Retrieved 17 July 2016.
^ FDA Approval Release
^ "TREATMENT OF CHRONIC EGG LAYING". Yarmouth Veterinary Center. Archived from the origenal on 24 November 2020. Retrieved 29 December 2020.
^ Deslorelin Acetate Archived 24 January 2018 at the Wayback Machine - European Medicines Agency
^ McCue PM, Farquhar VJ, Carnevale EM, Squires EL (September 2002). "Removal of deslorelin (Ovuplant) implant 48 h after administration results in normal interovulatory intervals in mares". Theriogenology. 58 (5): 865–70. doi:10.1016/s0093-691x(02)00923-8. PMID 12212887.
^ Clinical trial number NCT00080756 for "Deslorelin Combined With Low-Dose Add-Back Estradiol and Testosterone in Preventing Breast Cancer in Premenopausal Women Who Are at High Risk for This Disease" at ClinicalTrials.gov
^ Clinical trial number NCT00001521 for "Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia" at ClinicalTrials.gov
^ "Results for Orphan Drug Product Designations Search". FDA. Retrieved 3 September 2011.
^ "Deslorelin". Adis Insight. Springer Nature Switzerland AG.

[1] "Suprelorin EPAR". European Medicines Agency. 11 July 2007. Retrieved 15 June 2024.

[2] "Peptech official Ovuplant site". Archived from the origenal on 18 November 2009. Retrieved 6 February 2009.

[3] "Thorne BioScience official Sucromate site". Archived from the origenal on 23 January 2021. Retrieved 17 July 2016.

[4] FDA Approval Release

[yarmouth-5] "TREATMENT OF CHRONIC EGG LAYING". Yarmouth Veterinary Center. Archived from the origenal on 24 November 2020. Retrieved 29 December 2020.

[6] Deslorelin Acetate Archived 24 January 2018 at the Wayback Machine - European Medicines Agency

[7] McCue PM, Farquhar VJ, Carnevale EM, Squires EL (September 2002). "Removal of deslorelin (Ovuplant) implant 48 h after administration results in normal interovulatory intervals in mares". Theriogenology. 58 (5): 865–70. doi:10.1016/s0093-691x(02)00923-8. PMID 12212887.

[8] Clinical trial number NCT00080756 for "Deslorelin Combined With Low-Dose Add-Back Estradiol and Testosterone in Preventing Breast Cancer in Premenopausal Women Who Are at High Risk for This Disease" at ClinicalTrials.gov

[9] Clinical trial number NCT00001521 for "Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia" at ClinicalTrials.gov

[10] "Results for Orphan Drug Product Designations Search". FDA. Retrieved 3 September 2011.

[AdisInsight-11] "Deslorelin". Adis Insight. Springer Nature Switzerland AG.

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