LEUPROLIDE

First approved in 1985

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C59H84N16O12
Molecular Weight	1209.3983
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@H](CC5=CNC=N5)NC(=O)[C@@H]6CCC(=O)N6

InChI

InChIKey=GFIJNRVAKGFPGQ-LIJARHBVSA-N

InChI=1S/C59H84N16O12/c1-6-63-57(86)48-14-10-22-75(48)58(87)41(13-9-21-64-59(60)61)68-51(80)42(23-32(2)3)69-52(81)43(24-33(4)5)70-53(82)44(25-34-15-17-37(77)18-16-34)71-56(85)47(30-76)74-54(83)45(26-35-28-65-39-12-8-7-11-38(35)39)72-55(84)46(27-36-29-62-31-66-36)73-50(79)40-19-20-49(78)67-40/h7-8,11-12,15-18,28-29,31-33,40-48,65,76-77H,6,9-10,13-14,19-27,30H2,1-5H3,(H,62,66)(H,63,86)(H,67,78)(H,68,80)(H,69,81)(H,70,82)(H,71,85)(H,72,84)(H,73,79)(H,74,83)(H4,60,61,64)/t40-,41-,42-,43+,44-,45-,46-,47-,48-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C59H84N16O12
Molecular Weight	1209.3983
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	9 / 9
E/Z Centers	3
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7533699
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/ppa/leuprolide.html | http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020011s040lbl.pdf | http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf

Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH or LH-RH). The analog possesses greater potency than the natural hormone. It acts primarily on the anterior pituitary, inducing a transient early rise in gonadotrophin release. With continued use, leuprorelin causes pituitary desensitisation and/or down-regulation, leading to suppressed circulating levels of gonadotrophins and sex hormones. Leuprolide acetate used to treat a wide range of sex hormone-related disorders including advanced prostatic cancer, uterine leiomyomata (fibroids), endometriosis and precocious puberty.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gonadotropin-releasing hormone receptor 41 Target ID: CHEMBL1855 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7533699	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 178 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	Palliative	Approved 8429	LUPRON Approved Use LEUPROLIDE ACETATE INJECTION is indicated in the palliative treatment of advanced prostatic cancer. Launch Date 4.81852785E11
Endometriosis 32 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020011s040lbl.pdf	Primary	Approved 8429	LUPRON DEPOT Approved Use Endometriosis LUPRON DEPOT 3.75 mg is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions. LUPRON DEPOT monthly with norethindrone acetate 5 mg daily is also indicated for initial management of endometriosis and for management of recurrence of symptoms. (Refer also to norethindrone acetate prescribing information for WARNINGS, PRECAUTIONS, CONTRAINDICATIONS and ADVERSE REACTIONS associated with norethindrone acetate). Duration of initial treatment or retreatment should be limited to 6 months. Uterine Leiomyomata (Fibroids) LUPRON DEPOT 3.75 mg concomitantly with iron therapy is indicated for the preoperative hematologic improvement of patients with anemia caused by uterine leiomyomata. The clinician may wish to consider a one-month trial period on iron alone inasmuch as some of the patients will respond to iron alone. (See Table 1.) LUPRON may be added if the response to iron alone is considered inadequate. Recommended duration of therapy with LUPRON DEPOT 3.75 mg is up to three months. Experience with LUPRON DEPOT in females has been limited to women 18 years of age and older. Launch Date 8.1457919E11
Uterine leiomyomata 8 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020011s040lbl.pdf	Primary	Approved 8429	LUPRON DEPOT Approved Use Endometriosis LUPRON DEPOT 3.75 mg is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions. LUPRON DEPOT monthly with norethindrone acetate 5 mg daily is also indicated for initial management of endometriosis and for management of recurrence of symptoms. (Refer also to norethindrone acetate prescribing information for WARNINGS, PRECAUTIONS, CONTRAINDICATIONS and ADVERSE REACTIONS associated with norethindrone acetate). Duration of initial treatment or retreatment should be limited to 6 months. Uterine Leiomyomata (Fibroids) LUPRON DEPOT 3.75 mg concomitantly with iron therapy is indicated for the preoperative hematologic improvement of patients with anemia caused by uterine leiomyomata. The clinician may wish to consider a one-month trial period on iron alone inasmuch as some of the patients will respond to iron alone. (See Table 1.) LUPRON may be added if the response to iron alone is considered inadequate. Recommended duration of therapy with LUPRON DEPOT 3.75 mg is up to three months. Experience with LUPRON DEPOT in females has been limited to women 18 years of age and older. Launch Date 8.1457919E11

C_max

Value	Dose	Co-administered	Analyte	Population
32.48 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27824264	11.25 mg single, subcutaneous dose: 11.25 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		LEUPROLIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
426.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27824264	11.25 mg single, subcutaneous dose: 11.25 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		LEUPROLIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019943s031,020011s038,020708s031lbl.pdf	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		LEUPROLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
54% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019943s031,020011s038,020708s031lbl.pdf	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		LEUPROLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
30 mg 1 times / month multiple, subcutaneous Highest studied dose Dose: 30 mg, 1 times / month Route: subcutaneous Route: multiple Dose: 30 mg, 1 times / month Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	unhealthy, adult n = 49 Health Status: unhealthy Condition: cancer Age Group: adult Sex: unknown Population Size: 49 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	Other AEs: Asthenia, General body pain... Other AEs: Asthenia (6 patients) General body pain (16 patients) Headache (5 patients) Injection site reaction (4 patients) Hot flashes (23 patients) Gastrointestinal disorder (NOS) (5 patients) Dehydration (4 patients) Edema (4 patients) Disorder joint (8 patients) Myalgia (4 patients) Vertigo (3 patients) Neuromuscular disorders (3 patients) Paresthesia (4 patients) Skin reaction (6 patients) Urinary tract disorder NOS (5 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf
7.5 mg 1 times / month multiple, subcutaneous Recommended Dose: 7.5 mg, 1 times / month Route: subcutaneous Route: multiple Dose: 7.5 mg, 1 times / month Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	unhealthy, adult n = 56 Health Status: unhealthy Condition: cancer Age Group: adult Sex: unknown Population Size: 56 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf	Other AEs: General body pain, Hot flashes... Other AEs: General body pain (13 patients) Hot flashes (32 patients) Gastrointestinal disorder (NOS) (8 patients) Edema (8 patients) Libido decreased (3 patients) Disorder urinary tract (7 patients) Impotence (3 patients) Atrophy testicular (3 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019010s033,019732s031s035s036,020517s024s028s029lbl.pdf

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6427	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6427
ChemicalBook	CB8398455	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8398455
MolPort	MolPort-006-069-430	https://www.molport.com/shop/molecule-link/MolPort-006-069-430
MolPort	MolPort-046-684-146	https://www.molport.com/shop/molecule-link/MolPort-046-684-146
eMolecules	30152588	https://www.emolecules.com/cgi-bin/more?vid=30152588
eMolecules	539933	https://www.emolecules.com/cgi-bin/more?vid=539933

PubMed

Title	Date	PubMed
Adverse effects of leuprolide acetate depot treatment.	1993 Feb	8425646
Angina and myocardial infarction with use of leuprolide acetate.	1994 Jul	8030717
[Effects of androgen regulation system on bladder carcinogenesis in male mice].	1995 Nov	8551710
Anxiety and mood disorders associated with gonadotropin-releasing hormone agonist therapy.	1997	9230649
Steroidal 'add-back' therapy in patients treated with GnRH agonists.	1998	9628521
Erectile function and nocturnal penile tumescence in patients with prostate cancer undergoing luteinizing hormone-releasing hormone agonist therapy.	1999 Jan	10221860
Macrophage Fcgamma receptors expression is altered by treatment with dopaminergic drugs.	1999 Mar	10075867
[Seizure exacerbation by the use of leuprorelin acetate for treatment of central precocious puberty in a female patient with symptomatic localization-related epilepsy].	1999 Sep	10576781
Uterine adenocarcinoma after GnRH agonist treatment.	2000 Feb	10763848
Pituitary haemorrhage after leuprolide therapy for prostatic cancer, clinically imitating acute subarachnoidal haemorrhage.	2002	12403969
Leuprolide-induced myopathy.	2002 Oct	12366635
Pituitary apoplexy after leuprolide injection for ovum donation.	2003 Jan	12507807
Treatment of leuprolide-induced depression with intramuscular testosterone: a case report.	2003 Mar	12716284
Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial.	2004 May	15142146
Leuprolide acetate suppresses pedophilic urges and arousability.	2005 Dec	16362253
Effects of gonadotrophin-releasing hormone agonists on apoptosis of granulosa cells.	2005 May	15965100
Pituitary apoplexy after leuprolide.	2006	16832587
A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders.	2006 Dec	17187010
Discovery of a pituitary adenoma following treatment with a gonadotropin-releasing hormone agonist in a patient with prostate cancer.	2006 Jan	16448441
Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902.	2007 Feb	17095587
[Ischemic stroke associated with LH-RH analogue (leuprorelin) administration in a young woman].	2007 May	17585607
A possible participation of gonadotropin-releasing hormone in the neuroleptic and cataleptic effect of haloperidol.	2009 Jun	19403167
Long-term effects of GnRH agonist, GnRH antagonist, and estrogen plus progesterone treatment on apoptosis related genes in rat ovary.	2009 May	18829022
Impacts of leuprolide acetate on quality of life in patients with prostate cancer: a prospective multicenter study.	2010 Dec	20707648
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
Testosterone regulates tight junction proteins and influences prostatic autoimmune responses.	2011 Jun	21761342

Patents

Sample Use Guides

In Vivo Use Guide

Dosing: Adult Prostate cancer, advanced: Note: Treatment is usually continued after development of metastatic (castration-resistant) disease. IM: Lupron Depot 7.5 mg (monthly): 7.5 mg every month or Lupron Depot 22.5 mg (3 month): 22.5 mg every 12 weeks or Lupron Depot 30 mg (4 month): 30 mg every 16 weeks or Lupron Depot 45 mg (6 month): 45 mg every 24 weeks SubQ: Eligard: 7.5 mg monthly or 22.5 mg every 3 months or 30 mg every 4 months or 45 mg every 6 months Leuprolide acetate 5 mg/mL solution: 1 mg daily Endometriosis: IM: Initial therapy may be with leuprolide alone or in combination with norethindrone; if re-treatment for an additional 6 months is necessary, concomitant norethindrone should be used. Re-treatment is not recommended for longer than one additional 6-month course. Lupron Depot: 3.75 mg every month for up to 6 months or Lupron Depot-3 month: 11.25 mg every 3 months for up to 2 doses (6 months total duration of treatment) Uterine leiomyomata (fibroids): IM (in combination with iron): Lupron Depot: 3.75 mg every month for up to 3 months or Lupron Depot-3 month: 11.25 mg as a single injection Breast cancer, premenopausal ovarian supression (off-label use): IM: Lupron Depot: 3.75 mg every 28 days for up to 24 months (Boccardo 1999) or Lupron Depot-3 month: 11.25 mg every 3 months for up to 24 months (Boccardo 1999; Schmid 2007) Treatment of paraphilia/hypersexuality (off-label use; Guay 2009; Reilly 2000): Males: IM: Note: May cause an initial increase in androgen concentrations which may be treated with an antiandrogen (eg, flutamide, cyproterone) for 1 to 2 months (Guay 2009). Avoid use in patients with osteoporosis or active pituitary pathology. SubQ: Test dose: 1 mg (observe for hypersensitivity) Depot IM: 3.75 to 7.5 mg monthly Dosing: Geriatric Refer to adult dosing. Dosing: Pediatric Precocious puberty (consider discontinuing by age 11 for females and by age 12 for males): IM: Lupron Depot-Ped (monthly): ≤25 kg: 7.5 mg every month >25 to 37.5 kg: 11.25 mg every month >37.5 kg: 15 mg every month Titrate dose upward in increments of 3.75 mg every 4 weeks if down-regulation is not achieved. Lupron Depot-Ped (3 month): 11.25 mg or 30 mg every 12 weeks SubQ (leuprolide acetate 5 mg/mL solution): Initial: 50 mcg/kg/day; titrate dose upward by 10 mcg/kg/day if down-regulation is not achieved. Note: Higher mg/kg doses may be required in younger children.

Route of Administration: Other

In Vitro Use Guide

In primary cell cultures from human prostate carcinoma leuprolide (from 5-20 ng/mL) showed a significant reduction in cell growth rate and an increase in DNA-fragmented cell number.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:53:43 UTC 2023` Edited by `admin` on `Sat Dec 16 16:53:43 UTC 2023`
Record UNII	EFY6W0M8TG
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEUPROLIDE

Common Name

English

LEUPRORELIN SLOW RELEASE

Common Name

English

leuprorelin [INN]

Common Name

English

LEUPROLIDE [HSDB]

Common Name

English

LEUPRORELIN

Official Name

English

TAP-144 FREE BASE

Code

English

Leuprorelin [WHO-DD]

Common Name

English

LEUPORELIN

Common Name

English

NSC-377526

Code

English

LEUPROLIDE [MI]

Common Name

English

LEUPROLIDE [VANDF]

Common Name

English

CKD-841

Code

English

ABBOTT-43818 FREE BASE

Code

English

(-)-LEUPROLIDE

Common Name

English

LEUPRORELIN [MART.]

Common Name

English

LEUPRORELIN [EP MONOGRAPH]

Common Name

English

5-OXO-L-PROLYL-L-HISTIDYL-L-TRYPTOPHYL-L-SERYL-L-TRYOSYL-D-LEUCYL-L-LEUCYL-L-ARGINYL-N-ETHYL-L-PROLINAMIDE

Common Name

English

PGLU-HIS-TRP-SER-TYR-D-LEU-LEU-ARG-PRO-NHC2H5

Common Name

English

Classification Tree Code System Code

WHO-ATC

L02AE51