Leuprolide

Identification

Name
Leuprolide
Accession Number
DB00007
Description

Leuprolide is a synthetic 9-residue peptide analogue of gonadotropin-releasing hormone (GnRH). Unlike the endogenous decapeptide GnRH, leuprolide contains a single D-amino acid (D-leucyl) residue, which helps to increase its circulating half-life from three to four minutes to approximately three hours.4 As a GnRH mimic, leuprolide is capable of binding to the GnRH receptor (GnRHR) and inducing downstream modulation of both gonadotropin hormone and sex steroid levels. Prolonged activation of GnRHR results in significant downregulation of sex steroid levels, which is primarily responsible for the clinical efficacy of leuprolide in diverse conditions, including advanced prostate cancer, endometriosis, and central precocious puberty.1,3

Leuprolide was first approved in 1985 as a daily subcutaneous injection under the tradename Lupron™ by Abbvie Endocrine Inc.11 Since this initial approval, various long-acting intramuscular and subcutaneous products have been developed such that patients can be dosed once every six months.6,9 Leuprolide remains frontline therapy in all conditions for which it is indicated for use.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 1209.3983
Monoisotopic: 1208.645462232
Chemical Formula
C59H84N16O12
Synonyms
  • Leuprorelin
  • Leuprorelina
  • Leuproreline
  • Leuprorelinum
External IDs
  • CKD-841

Pharmacology

Indication

Leuprolide is indicated for the palliative treatment of advanced prostate cancer6,9 as well as for the treatment of pediatric patients with central precocious puberty (CPP).7,8 In combination with oral norethisterone (also known as norethindrone), leuprolide is also indicated for the initial treatment of the symptoms of endometriosis.5 Finally, in combination with iron supplementation, leuprolide is indicated for the preoperative hematological improvement of anemic patients with uterine leiomyomata (uterine fibroids).10

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Leuprolide is a gonadotropin-releasing hormone (GnRH) analogue that functions as a GnRH receptor superagonist.3,4 After an initial spike in GnRH-mediated steroidal production, including testosterone and estradiol, prolonged use results in a significant drop in circulating steroid levels, in line with those produced through other forms of androgen-deprivation therapy (ADT).1,2,3 The corresponding hormonal/steroidal changes produce specific adverse effects in different patient populations.

In women undergoing treatment for endometriosis or uterine leiomyomata, careful consideration regarding pregnancy status is advised. The initial increase in estradiol levels may worsen symptoms such as pain and bleeding. Long-term use of leuprolide is associated with loss of bone mineral density. Patients co-administered with norethisterone may experience sudden vision loss, proptosis, diplopia, migraine, thrombophlebitis, and pulmonary embolism and may also be at higher risk of cardiovascular disease. Patients with a history of depression may experience severe recurrence of depressive symptoms.5,10

In men undergoing palliative treatment for advanced/metastatic prostate cancer, short-term spikes in testosterone levels may cause tumour flare and associated symptoms such as bone pain, hematuria, neuropathy, bladder and/or ureteral obstruction, and spinal cord compression. In addition, patients are at increased risk of developing hyperglycemia, diabetes, and cardiovascular disease, which may manifest through myocardial infarction, stroke, cardiac death, or prolonged QT/QTc interval. In addition, Leuprolide may cause convulsions and embryo-fetal toxicity.6,9

In pediatric patients undergoing treatment for central precocious puberty (CPP), the initial steroidal spike may be associated with increased clinical signs of puberty within 2-4 weeks of treatment initiation. In addition, leuprolide may cause convulsions and psychiatric symptoms, including irritability, impatience, aggression, anger, and crying.7,8

Mechanism of action

Gonadotropin-releasing hormone (GnRH) is a naturally occurring decapeptide that modulates the hypothalamic-pituitary-gonadal (HPG) axis. GnRH binds to corresponding receptors (GnRHRs) on the anterior pituitary gonadotropes, which in turn release luteinizing hormone (LH) and follicle-stimulating hormone (FSH); these, in turn, affect the downstream synthesis and release of the sex hormones testosterone, dihydrotestosterone, estrone, and estradiol.1,3

Despite the variety of conditions indicated for treatment with leuprolide, the mechanism of action underlying efficacy is the same in all cases. As a GnRHR agonist, leuprolide binds to and initially activates downstream LH and FSH release; this initial spike in gonadotropin levels is responsible for some of the adverse effects associated with treatment. After 2-4 weeks of treatment, continuous stimulation of GnRHR results in feedback inhibition and significant downregulation of LH, FSH, and their corresponding downstream effects, producing a therapeutic benefit. These effects are reversible upon treatment discontinuation.1,2,3,4,5,6,7,8,9,10

TargetActionsOrganism
AGonadotropin-releasing hormone receptor
agonist
Humans
Absorption

Leuprolide is typically administered as a single-dose long-acting formulation employing either microsphere or biodegradable solid depot technologies.1 Regardless of the exact formulation and initial dose strength, the Cmax is typically achieved by 4-5 hours post-injection and displays large variability in the range of 4.6 - 212 ng/mL. Eventual steady-state kinetics are typically achieved by four weeks, with a narrower range of 0.1 - 2 ng/mL. No studies on the effects of food on absorption have been carried out.5,6,7,8,9,10

Volume of distribution

Leuprolide has an apparent steady-state volume of distribution of 27 L following intravenous bolus administration to healthy males. The volume of distribution for indicated routes of subcutaneous or intramuscular injection has not been reported.5,6,7,8,9,10

Protein binding

Leuprolide displays in vitro binding to human plasma proteins between 43% and 49%.5,6,7,8,9,10

Metabolism

Radiolabeling studies suggest that leuprolide is primarily metabolized to inactive penta-, tri-, and dipeptide entities, which are likely further metabolized. It is expected that various peptidases encountered throughout systemic circulation are responsible for leuprolide metabolism.5,6,7,8,9,10

Route of elimination

Following administration of 3.75 mg leuprolide depot suspension to three patients, less than 5% of the initial dose was recovered as unchanged or pentapeptide metabolite in the urine.5,6,7,10

Half-life

Leuprolide has a terminal elimination half-life of approximately three hours.5,6,7,8,9,10

Clearance

Leuprolide administered as a 1 mg intravenous bolus in healthy males has a mean systemic clearance between 7.6 and 8.3 L/h.5,6,7,8,9,10

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Leuprolide is considered extremely safe, with low dose-related toxicity and comparatively mild adverse effects.1 Prostate cancer patients treated with leuprolide at doses as high as 20 mg/day for two years showed no additional adverse effects compared to those receiving 1 mg/day.10

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirLeuprolide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Leuprolide.
AcebutololThe risk or severity of QTc prolongation can be increased when Leuprolide is combined with Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of Leuprolide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Leuprolide which could result in a higher serum level.
AcetaminophenLeuprolide may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Leuprolide which could result in a lower serum level and potentially a reduction in efficacy.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Leuprolide.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Leuprolide which could result in a higher serum level.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Leuprolide is combined with Acipimox.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
No interactions found.

Products

Product Ingredients
IngredientUNIICASInChI Key
Leuprolide acetate37JNS02E7V74381-53-6YFDMUNOZURYOCP-XNHQSDQCSA-N
International/Other Brands
Leuplin (Takeda) / LeuProMaxx (Baxter/Teva) / Memryte (Curaxis) / Prostap 3 (Takeda UK) / Prostap SR (Takeda UK)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EligardKit45 mg/0.375mLSubcutaneousSanofi Aventis2002-01-232016-05-31US flag
EligardKit7.5 mg/0.25mLSubcutaneousTOLMAR PHARMACEUTICALS INC.2002-05-15Not applicableUS flag
EligardKit30 mg/0.5mLSubcutaneousTOLMAR PHARMACEUTICALS INC.2002-01-232015-05-08US flag
EligardKit30 mg/0.5mLSubcutaneousTOLMAR PHARMACEUTICALS INC.2003-02-26Not applicableUS flag
EligardKit7.5 mg/0.25mLSubcutaneousSanofi Aventis2002-01-232016-05-31US flag
EligardInjection, powder, for suspension, extended release22.5 mgSubcutaneousSanofi Aventis2003-12-01Not applicableCanada flag
EligardKit30 mg/0.5mLSubcutaneousSanofi Aventis2002-01-232016-05-31US flag
EligardKit22.5 mg/0.375mLSubcutaneousTOLMAR PHARMACEUTICALS INC.2002-01-232015-05-08US flag
EligardKit22.5 mg/0.375mLSubcutaneousTOLMAR PHARMACEUTICALS INC.2002-08-26Not applicableUS flag
EligardInjection, powder, for suspension, extended release45 mgSubcutaneousSanofi Aventis2005-08-15Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Leuprolide AcetateKit1 mg/0.2mLSubcutaneous; TopicalTeva Parenteral Medicines, Inc.2000-11-062011-03-31US flag
Leuprolide AcetateInjection, solution1 mg/.2mLSubcutaneousEon Labs, Inc.1998-08-04Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Leuprolide AcetateLeuprolide acetate (1 mg/0.2mL) + Isopropyl alcohol (0.7 mL/1)KitSubcutaneous; TopicalGenzyme Corporation2001-11-292010-03-31US flag
Leuprolide AcetateLeuprolide acetate + Isopropyl alcoholKitSubcutaneous; TopicalGenzyme Corporation2006-05-312006-05-31US flag
Leuprolide AcetateLeuprolide acetate (1 mg/0.2mL) + Isopropyl alcohol (0.7 mL/1mL)KitSubcutaneous; TopicalSandoz Inc1998-08-04Not applicableUS flag
Leuprolide AcetateLeuprolide acetate (5 mg/1mL) + Isopropyl alcohol (0.7 mL/1mL)KitSubcutaneous; TopicalSun Pharma Global Inc.2014-12-152015-08-31US flag
Leuprolide AcetateLeuprolide acetate (5 mg/1mL) + Isopropyl alcohol (0.7 mL/1mL)KitSubcutaneous; TopicalSun Pharmaceutical Industries, Inc.2014-12-15Not applicableUS flag
Lupaneta PackLeuprolide acetate (11.25 mg/1.5mL) + Isopropyl alcohol (0.7 mL/1mL) + Norethisterone acetate (5 mg/1)Intramuscular; Oral; TopicalAbbVie Inc.2013-07-01Not applicableUS flag
Lupaneta PackLeuprolide acetate (3.75 mg/1mL) + Ethanol (0.7 mL/1mL) + Norethisterone acetate (5 mg/1)Intramuscular; Oral; TopicalAbbVie Inc.2013-07-01Not applicableUS flag
Lupron DepotLeuprolide acetate (3.75 mg/1mL) + Isopropyl alcohol (0.7 mL/1mL)KitIntramuscular; TopicalAbbVie Inc.1990-10-22Not applicableUS flag
ViadurLeuprolide acetate (72 mg/1) + Lidocaine hydrochloride (20 mg/1mL)KitSubcutaneous; TopicalBayer Pharmaceuticals Corporation2006-05-10Not applicableUS flag

Categories

ATC Codes
L02AE51 — Leuprorelin and bicalutamideL02AE02 — Leuprorelin
Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
EFY6W0M8TG
CAS number
53714-56-0
InChI Key
GFIJNRVAKGFPGQ-LIJARHBVSA-N
InChI
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
IUPAC Name
(2S)-1-[(2S)-5-carbamimidamido-2-[(2S)-2-[(2R)-2-[(2S)-2-[(2S)-3-hydroxy-2-[(2S)-2-[(2S)-3-(1H-imidazol-4-yl)-2-{[(2S)-5-oxopyrrolidin-2-yl]formamido}propanamido]-3-(1H-indol-3-yl)propanamido]propanamido]-3-(4-hydroxyphenyl)propanamido]-4-methylpentanamido]-4-methylpentanamido]pentanoyl]-N-ethylpyrrolidine-2-carboxamide
SMILES
CCNC(=O)[[email protected]@H]1CCCN1C(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]](CC(C)C)NC(=O)[[email protected]@H](CC(C)C)NC(=O)[[email protected]](CC1=CC=C(O)C=C1)NC(=O)[[email protected]](CO)NC(=O)[[email protected]](CC1=CNC2=C1C=CC=C2)NC(=O)[[email protected]](CC1=CNC=N1)NC(=O)[[email protected]@H]1CCC(=O)N1

References

Synthesis Reference

Daniel Kadzimirzs, Gerhard Jas, Volker Autze, "Solution-Phase Synthesis of Leuprolide and Its Intermediates." U.S. Patent US20090005535, issued January 01, 2009.

US20090005535
General References
  1. Hoda MR, Kramer MW, Merseburger AS, Cronauer MV: Androgen deprivation therapy with Leuprolide acetate for treatment of advanced prostate cancer. Expert Opin Pharmacother. 2017 Jan;18(1):105-113. doi: 10.1080/14656566.2016.1258058. Epub 2016 Nov 28. [PubMed:27826989]
  2. Ali M, Chaudhry ZT, Al-Hendy A: Successes and failures of uterine leiomyoma drug discovery. Expert Opin Drug Discov. 2018 Feb;13(2):169-177. doi: 10.1080/17460441.2018.1417381. Epub 2017 Dec 18. [PubMed:29254389]
  3. Wilson AC, Meethal SV, Bowen RL, Atwood CS: Leuprolide acetate: a drug of diverse clinical applications. Expert Opin Investig Drugs. 2007 Nov;16(11):1851-63. doi: 10.1517/13543784.16.11.1851. [PubMed:17970643]
  4. Conn PM, Crowley WF Jr: Gonadotropin-releasing hormone and its analogues. N Engl J Med. 1991 Jan 10;324(2):93-103. doi: 10.1056/NEJM199101103240205. [PubMed:1984190]
  5. FDA Approved Drug Products: Lupaneta Pack for intramuscular and oral use [Link]
  6. FDA Approved Drug Products: Lupron Depot (leuprolide acetate) depot suspension [Link]
  7. FDA Approved Drug Products: Lupron Depot-Ped (leuprolide acetate) depot suspension [Link]
  8. FDA Approved Drug Products: Fensolvi (leuprolide acetate) suspension [Link]
  9. FDA Approved Drug Products: Eligard (leuprolide acetate) suspension [Link]
  10. FDA Approved Drug Products: Lupron Depot 3.75mg (leuprolide acetate) depot suspension [Link]
  11. FDA Approved Drug Products: Lupron (leuprolide) injection; discontinued [Link]
Human Metabolome Database
HMDB0041916
KEGG Drug
D08113
KEGG Compound
C07612
PubChem Substance
46507635
ChemSpider
571356
BindingDB
50369395
RxNav
42375
ChEBI
6427
ChEMBL
CHEMBL1201199
Therapeutic Targets Database
DAP000020
PharmGKB
PA450203
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Leuprorelin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
  • 68:18.08 — Gonadotropins
FDA label
Download (477 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableEffect of Two Protocols of Ovarian Stimulation on Oocyte Quality1
4CompletedNot AvailableEndometriosis1
4CompletedNot AvailableProstate Cancer1
4CompletedBasic ScienceContraception / Fertility1
4CompletedBasic ScienceDepression / Hot Flushes / Menopause1
4CompletedBasic ScienceHot Flushes1
4CompletedPreventionOvarian Hyperstimulation Syndrome1
4CompletedTreatmentCentral Precocious Puberty (CPP)3
4CompletedTreatmentEgg Donation1
4CompletedTreatmentEndometriosis / Infertility1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Abbott Laboratories Ltd.
  • Cardinal Health
  • Eon Labs
  • Hospira Inc.
  • Oso Biopharmaceuticals Manufacturing LLC
  • Physicians Total Care Inc.
  • Sanofi-Aventis Inc.
  • Sun Pharmaceutical Industries Ltd.
  • Takeda Pharmaceutical Co. Ltd.
  • Teva Pharmaceutical Industries Ltd.
  • Tolmar Inc.
Dosage Forms
FormRouteStrength
Injection, powder, for solution
Injection, powder, for solutionParenteral22.5 MG
Injection, powder, for solutionParenteral45 MG
Injection, powder, for solutionParenteral7.5 MG
Injection, powder, for suspension, extended releaseSubcutaneous22.5 mg
Injection, powder, for suspension, extended releaseSubcutaneous30 mg
Injection, powder, for suspension, extended releaseSubcutaneous45 mg
Injection, powder, for suspension, extended releaseSubcutaneous7.5 mg
Injection, suspension, extended release22.5 mg
Injection, suspension, extended release45 mg
Injection, suspension, extended release7.5 mg
KitSubcutaneous22.5 mg/0.375mL
KitSubcutaneous30 mg/0.5mL
KitSubcutaneous45 mg/0.375mL
KitSubcutaneous7.5 mg/0.25mL
Injection, powder, for suspensionSubcutaneous45 mg
Injection22.5 mg
Injection45 mg
Injection7.5 mg
Injection, powder, for suspensionSubcutaneous22.5 mg
Injection, powder, for suspensionSubcutaneous7.5 mg
InjectionIntramuscular3.75 MG
Injection, powder, for suspensionParenteral11.25 MG/ML
Injection, powder, for suspensionParenteral3.75 MG/ML
Injection, powder, for suspension, extended release11.25 MG/2ML
Injection, powder, for suspension, extended release3.75 MG/2ML
Injection, solutionCutaneous1 MG/0.2ML
Injection, solutionSubcutaneous1 mg/0.2ml
Injection, suspension, extended release1.88 mg
Injection, suspension, extended release11.25 mg
Injection, suspension, extended release3.75 mg
PowderIntramuscular22.5 mg
PowderIntramuscular7.5 mg
ImplantParenteral3.6 MG
ImplantParenteral5 MG
Injection, solutionSubcutaneous1 mg/.2mL
KitSubcutaneous; Topical1 mg/0.2mL
LiquidSubcutaneous
Implant3.6 mg
Implant5 mg
Suspension
Injection, solution5 mg/ml
Injection, powder, lyophilized, for solutionIntramuscular; Subcutaneous3.75 mg
Injection, powder, lyophilized, for solutionIntramuscular; Subcutaneous11.25 mg
Injection
KitSubcutaneous; Topical5 mg/1mL
SolutionSubcutaneous5 mg
Injection, powder, for suspension, extended releaseIntramuscular11.25 mg
Injection, powder, for suspension, extended releaseIntramuscular15 mg
Injection, powder, for suspension, extended releaseIntramuscular22.5 mg
Injection, powder, for suspension, extended releaseIntramuscular3.75 mg
Injection, powder, for suspension, extended releaseIntramuscular30 mg
Injection, powder, for suspension, extended releaseIntramuscular7.5 mg
Injection, powder, lyophilized, for suspensionIntramuscular3.75 mg/1mL
Injection, powder, lyophilized, for suspensionIntramuscular30 mg/1.5mL
KitIntramuscular; Topical
KitIntramuscular; Topical11.25 mg/1.5mL
KitIntramuscular; Topical22.5 mg/1.5mL
KitIntramuscular; Topical3.75 mg/1mL
KitIntramuscular; Topical30 mg/1.5mL
KitIntramuscular; Topical45 mg/1.5mL
KitIntramuscular; Topical7.5 mg/1mL
Injection, powder, lyophilized, for suspensionIntramuscular11.25 mg/1mL
Injection, powder, lyophilized, for suspensionIntramuscular15 mg/1mL
Injection, powder, lyophilized, for suspensionIntramuscular7.5 mg/1mL
KitIntramuscular; Topical11.25 mg/1mL
Injection, powder, for suspensionParenteral22.5 mg
Injection, powder, for suspensionParenteral3.75 mg
Injection, powder, for suspension3.75 MG
Injection, powder, for suspension, extended releaseParenteral22.5 MG
Injection, solutionSubcutaneous5 mg/ml
KitSubcutaneous; Topical
Injection, powder, for suspension, extended release; kitIntramuscular
Prices
Unit descriptionCostUnit
Eligard 45 mg syringe2959.2USD syringe
Eligard 30 mg syringe1972.8USD syringe
Eligard 22.5 mg syringe1479.6USD syringe
Lupron 2-wk 1 mg/0.2 ml kit594.37USD kit
Eligard 7.5 mg syringe493.2USD syringe
Leuprolide Acetate 1 mg/0.2ml Kit 2.8ml 2-Week Kit400.74USD box
Leuprolide 2wk 1 mg/0.2 ml kit385.33USD kit
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6036976No2000-03-142016-12-13US flag
US8921326No2014-12-302031-02-05US flag
US7429559No2008-09-302019-01-13US flag
US8815801No2014-08-262022-06-28US flag
US5728396No1998-03-172017-01-30US flag
US6156331No2000-12-052017-01-30US flag
US6375978No2002-04-232018-12-17US flag
US6235712No2001-05-222017-06-13US flag
US6113938No2000-09-052018-07-24US flag
US6124261No2000-09-262017-06-13US flag
US6395292No2002-05-282017-01-30US flag
US6132420No2000-10-172017-01-30US flag
US5985305No1999-11-162017-01-30US flag
US5932547No1999-08-032017-06-13US flag
US6565874No2003-05-202018-10-28US flag
US6773714No2004-08-102018-10-28US flag
US6626870No2003-09-302020-03-27US flag
US9283282No2016-03-152018-10-28US flag
US9254307No2016-02-092018-10-28US flag
US8486455No2013-07-162018-10-28US flag
US8840916No2014-09-232020-11-13US flag
US8470359No2013-06-252023-10-15US flag
US9539333No2017-01-102020-11-13US flag
US9914802No2018-03-132020-11-13US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)150-155https://www.trc-canada.com/product-detail/?L330600
pKa9.6http://products.sanofi.ca/en/eligard.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.0338 mg/mLALOGPS
logP1.04ALOGPS
logP-2.4ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)9.49ChemAxon
pKa (Strongest Basic)11.92ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count16ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area429.04 Å2ChemAxon
Rotatable Bond Count32ChemAxon
Refractivity327.24 m3·mol-1ChemAxon
Polarizability126.8 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Peptide binding
Specific Function
Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone...
Gene Name
GNRHR
Uniprot ID
P30968
Uniprot Name
Gonadotropin-releasing hormone receptor
Molecular Weight
37730.355 Da
References
  1. Castellon E, Clementi M, Hitschfeld C, Sanchez C, Benitez D, Saenz L, Contreras H, Huidobro C: Effect of leuprolide and cetrorelix on cell growth, apoptosis, and GnRH receptor expression in primary cell cultures from human prostate carcinoma. Cancer Invest. 2006 Apr-May;24(3):261-8. [PubMed:16809153]
  2. Borroni R, Di Blasio AM, Gaffuri B, Santorsola R, Busacca M, Vigano P, Vignali M: Expression of GnRH receptor gene in human ectopic endometrial cells and inhibition of their proliferation by leuprolide acetate. Mol Cell Endocrinol. 2000 Jan 25;159(1-2):37-43. [PubMed:10687850]
  3. Imai A, Takagi A, Horibe S, Takagi H, Tamaya T: Fas and Fas ligand system may mediate antiproliferative activity of gonadotropin-releasing hormone receptor in endometrial cancer cells. Int J Oncol. 1998 Jul;13(1):97-100. [PubMed:9625809]
  4. Murase M, Uemura T, Gao M, Inada M, Funabashi T, Hirahara F: GnRH antagonist-induced down-regulation of the mRNA expression of pituitary receptors: comparisons with GnRH agonist effects. Endocr J. 2005 Feb;52(1):131-7. [PubMed:15758569]
  5. Khurana KK, Singh SB, Tatum AH, Schulz V, Badawy SZ: Maintenance of increased Bcl-2 expression in uterine leiomyomas after GnRH agonist therapy. J Reprod Med. 1999 Jun;44(6):487-92. [PubMed:10394541]
  6. FDA Approved Drug Products: Lupaneta Pack for intramuscular and oral use [Link]
  7. FDA Approved Drug Products: Lupron Depot (leuprolide acetate) depot suspension [Link]
  8. FDA Approved Drug Products: Lupron Depot-Ped (leuprolide acetate) depot suspension [Link]
  9. FDA Approved Drug Products: Fensolvi (leuprolide acetate) suspension [Link]
  10. FDA Approved Drug Products: Eligard (leuprolide acetate) suspension [Link]
  11. FDA Approved Drug Products: Lupron Depot 3.75mg (leuprolide acetate) depot suspension [Link]

Drug created on June 13, 2005 07:24 / Updated on October 27, 2020 11:12

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