Degarelix

Identification

Name

Degarelix

Accession Number

DB06699

Description

Degarelix is used for the treatment of advanced prostate cancer. Degarelix is a synthetic peptide derivative drug which binds to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland and blocks interaction with GnRH. This antagonism reduces luteinising hormone (LH) and follicle-stimulating hormone (FSH) which ultimately causes testosterone suppression. Reduction in testosterone is important in treating men with advanced prostate cancer. Chemically, it is a synthetic linear decapeptide amide with seven unnatural amino acids, five of which are D-amino acids. FDA approved on December 24, 2008.

Type

Small Molecule

Groups

Approved

Structure

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MOLSDFPDBSMILESInChI

Similar Structures

Structure for Degarelix (DB06699)

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Weight

Average: 1632.29
Monoisotopic: 1630.748797

Chemical Formula

C₈₂H₁₀₃ClN₁₈O₁₆

Synonyms

• Degarelix

External IDs

• FE200486

Pharmacology

Indication

Degaralix is used for the management of advanced prostate cancer.

Associated Conditions

• Advanced Prostate Cancer

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

Degarelix is a synthetic derivative of GnRH decapeptide, the ligand of the GnRH receptor. Gonadotropin and androgen production result from the binding of endogenous GnRH to the GnRH receptor. Degarelix antagonizes the GnRH receptor which in turn blocks the release of LH and FSH from the pituitary. LF and FSH decreases in a concentration-dependent manner. The reduction in LH leads to a decrease in testosterone release from the testes.

Mechanism of action

Degarelix competitively inhibits GnRH receptors in the pituitary gland, preventing the release of luteinizing hormone (LH) and follicle stimulating hormone. Reduced LH suppresses testosterone release, which slows the growth and reduces the size of prostate cancers.

Target	Actions	Organism
AGonadotropin-releasing hormone receptor	antagonist	Humans

Absorption

Degarelix forms a depot at the site of injection after subcutaneous administration from which the drug slowly released into circulation. After a single bolus dose of 2mg/kg, peak plasma concentrations of degarelix occured within 6 hours at a concentration of 330 ng/mL. Ki = 0.082 ng/mL and 93% of receptors were fully suppressed; MRT = 4.5 days.

Volume of distribution

Central compartment: 8.88 - 11.4 L; Peripheral compartment: 40.9 L

Protein binding

90% of the drug is bound to plasma proteins.

Metabolism

70% - 80% of degarelix is subject to peptide hydrolysis during its passage through the hepatobiliary system and then fecally eliminated. No active or inactive metabolites or involvement of CYP450 isozymes.

Route of elimination

Fecal (70% to 80%) and renal (20%-30% of unchanged drug)

Half-life

Terminal half-life: 41.5 - 70.2 days; Absorption half-life: 32.9 hours; Half-life from injection site: 1.17 days.

Clearance

Following subcutaneous administration of degarelix to prostate cancer patients the clearance is approximately 9 L/hr.

Adverse Effects

Learn about our commercial Adverse Effects data.

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Toxicity

The most commonly observed adverse reactions (> 10%) during degarelix therapy included injection site reactions (e.g., pain, erythema, swelling, or induration), hot flashes, increased weight, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Acebutolol	The risk or severity of QTc prolongation can be increased when Degarelix is combined with Acebutolol.
Acrivastine	The risk or severity of QTc prolongation can be increased when Degarelix is combined with Acrivastine.
Adenosine	The risk or severity of QTc prolongation can be increased when Degarelix is combined with Adenosine.
Ajmaline	The risk or severity of QTc prolongation can be increased when Ajmaline is combined with Degarelix.
Alfuzosin	The risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Degarelix.
Alimemazine	The risk or severity of QTc prolongation can be increased when Alimemazine is combined with Degarelix.
Amantadine	The risk or severity of QTc prolongation can be increased when Amantadine is combined with Degarelix.
Amifampridine	The risk or severity of QTc prolongation can be increased when Degarelix is combined with Amifampridine.
Amiodarone	The risk or severity of QTc prolongation can be increased when Degarelix is combined with Amiodarone.
Amisulpride	The risk or severity of QTc prolongation can be increased when Amisulpride is combined with Degarelix.

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
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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Food Interactions

No interactions found.

Products

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Degarelix acetate hydrate	EXT215F4ZU	934246-14-7	AUTFSFUMNFDPLH-KYMMNHPFSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Unlock Additional Data
Firmagon	Injection, powder, for solution	120 mg	Subcutaneous	Ferring Pharmaceuticals	2009-02-17	Not applicable
Firmagon	Powder, for solution	120 mg	Subcutaneous	Ferring Pharmaceuticals	2009-11-24	Not applicable
Firmagon	Powder, metered	40 mg/1mL	Subcutaneous	Ferring Pharmaceuticals	2009-03-02	2015-03-31
Firmagon		40 mg/1mL	Subcutaneous	Ferring Pharmaceuticals Inc.	2009-03-02	Not applicable
Firmagon	Powder, for solution	80 mg	Subcutaneous	Ferring Pharmaceuticals	2009-11-24	Not applicable
Firmagon	Injection, powder, for solution	80 mg	Subcutaneous	Ferring Pharmaceuticals	2009-02-17	Not applicable
Firmagon	Powder, metered	20 mg/1mL	Subcutaneous	Ferring Pharmaceuticals	2009-03-02	2015-03-31
Firmagon	Injection, powder, for solution	80 mg	Subcutaneous	Ferring Pharmaceuticals	2009-02-17	Not applicable
Firmagon		20 mg/1mL	Subcutaneous	Ferring Pharmaceuticals Inc.	2009-03-02	Not applicable

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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Categories

ATC Codes

L02BX02 — Degarelix

• L02BX — Other hormone antagonists and related agents
• L02B — HORMONE ANTAGONISTS AND RELATED AGENTS
• L02 — ENDOCRINE THERAPY
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• Amino Acids, Peptides, and Proteins
• Antineoplastic Agents
• Antineoplastic and Immunomodulating Agents
• Endocrine Therapy
• Gonadotropin-releasing Hormone Antagonists
• Gonadotropin-Releasing Hormone, antagonists & inhibitors
• Hormone Antagonists and Related Agents
• Peptides
• Potential QTc-Prolonging Agents
• QTc Prolonging Agents

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.

Kingdom

Organic compounds

Super Class

Organic Polymers

Class

Polypeptides

Sub Class

Not Available

Direct Parent

Polypeptides

Alternative Parents

Peptides / Phenylalanine and derivatives / Leucine and derivatives / N-acyl-alpha amino acids and derivatives / Proline and derivatives / Serine and derivatives / Alpha amino acid amides / Alanine and derivatives / N-phenylureas / Naphthalenes / Amphetamines and derivatives / Anilides / Pyrrolidinecarboxamides / N-acylpyrrolidines / N-arylamides / Pyrimidones / N-acyl ureas / Chlorobenzenes / N-acyl amines / Diazinanes / Aryl chlorides / Pyridines and derivatives / Tertiary carboxylic acid amides / Acetamides / Heteroaromatic compounds / Dicarboximides / Secondary carboxylic acid amides / Primary carboxylic acid amides / Dialkylamines / Azacyclic compounds / Primary alcohols / Hydrocarbon derivatives / Organic oxides / Organochlorides / Organopnictogen compounds / Carbonyl compounds

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Substituents

1,3-diazinane / Acetamide / Alanine or derivatives / Alcohol / Alpha peptide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Amphetamine or derivatives / Anilide / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Chlorobenzene / Dicarboximide / Fatty acyl / Fatty amide / Halobenzene / Heteroaromatic compound / Hydrocarbon derivative / Leucine or derivatives / Monocyclic benzene moiety / N-acyl urea / N-acyl-alpha amino acid or derivatives / N-acyl-amine / N-acylpyrrolidine / N-arylamide / N-phenylurea / N-substituted-alpha-amino acid / Naphthalene / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organochloride / Organohalogen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Phenylalanine or derivatives / Polypeptide / Primary alcohol / Primary carboxylic acid amide / Proline or derivatives / Pyridine / Pyrimidine / Pyrimidone / Pyrrolidine / Pyrrolidine carboxylic acid or derivatives / Pyrrolidine-2-carboxamide / Secondary aliphatic amine / Secondary amine / Secondary carboxylic acid amide / Serine or derivatives / Tertiary carboxylic acid amide / Urea / Ureide

show 54 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Chemical Identifiers

UNII

SX0XJI3A11

CAS number

214766-78-6

InChI Key

MEUCPCLKGZSHTA-XYAYPHGZSA-N

InChI

InChI=1S/C82H103ClN18O16/c1-45(2)35-60(72(107)92-59(16-9-10-33-87-46(3)4)80(115)101-34-12-17-68(101)79(114)88-47(5)70(84)105)93-74(109)63(38-51-23-30-58(31-24-51)91-81(85)116)95-76(111)64(39-50-21-28-57(29-22-50)90-71(106)66-42-69(104)100-82(117)99-66)97-78(113)67(44-102)98-77(112)65(41-53-13-11-32-86-43-53)96-75(110)62(37-49-19-26-56(83)27-20-49)94-73(108)61(89-48(6)103)40-52-18-25-54-14-7-8-15-55(54)36-52/h7-8,11,13-15,18-32,36,43,45-47,59-68,87,102H,9-10,12,16-17,33-35,37-42,44H2,1-6H3,(H2,84,105)(H,88,114)(H,89,103)(H,90,106)(H,92,107)(H,93,109)(H,94,108)(H,95,111)(H,96,110)(H,97,113)(H,98,112)(H3,85,91,116)(H2,99,100,104,117)/t47-,59+,60+,61-,62-,63-,64+,65-,66+,67+,68+/m1/s1

IUPAC Name

(4S)-N-{4-[(2S)-2-{[(1R)-2-[4-(carbamoylamino)phenyl]-1-{[(1S)-1-{[(2S)-1-[(2S)-2-{[(1R)-1-carbamoylethyl]carbamoyl}pyrrolidin-1-yl]-1-oxo-6-[(propan-2-yl)amino]hexan-2-yl]carbamoyl}-3-methylbutyl]carbamoyl}ethyl]carbamoyl}-2-[(2S)-2-[(2R)-2-[(2R)-3-(4-chlorophenyl)-2-[(2R)-2-acetamido-3-(naphthalen-2-yl)propanamido]propanamido]-3-(pyridin-3-yl)propanamido]-3-hydroxypropanamido]ethyl]phenyl}-2,6-dioxo-1,3-diazinane-4-carboxamide

SMILES

CC(C)C[[email protected]](NC(=O)[[email protected]@H](CC1=CC=C(NC(N)=O)C=C1)NC(=O)[[email protected]](CC1=CC=C(NC(=O)[[email protected]@H]2CC(=O)NC(=O)N2)C=C1)NC(=O)[[email protected]](CO)NC(=O)[[email protected]@H](CC1=CC=CN=C1)NC(=O)[[email protected]@H](CC1=CC=C(Cl)C=C1)NC(=O)[[email protected]@H](CC1=CC=C2C=CC=CC2=C1)NC(C)=O)C(=O)N[[email protected]@H](CCCCNC(C)C)C(=O)N1CCC[[email protected]]1C(=O)N[[email protected]](C)C(N)=O

References

Synthesis Reference

Carin WINDERSTROM, "KIT AND METHOD FOR PREPARATION OF A DEGARELIX SOLUTION." U.S. Patent US20100286603, issued November 11, 2010.

US20100286603

General References

1. Steinberg M: Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancer. Clin Ther. 2009;31 Pt 2:2312-31. doi: 10.1016/j.clinthera.2009.11.009. [PubMed:20110043]
2. Persson BE, Kold Olesen T, Jensen JK: Degarelix: a new approach for the treatment of prostate cancer. Neuroendocrinology. 2009;90(3):235-44. doi: 10.1159/000228832. Epub 2009 Jul 14. [PubMed:19602868]

External Links

KEGG Drug

D08901

PubChem Compound

16136245

PubChem Substance

99443253

ChemSpider

17292756

BindingDB

50102450

RxNav

475230

ChEBI

135961

ChEMBL

CHEMBL415606

PharmGKB

PA165958373

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Degarelix

AHFS Codes

• 10:00.00 — Antineoplastic Agents
• 92:40.00 — Gonadotropin-releasing Hormone Antagonists

FDA label

Download (448 KB)

MSDS

Download (479 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Prostate Cancer	1
4	Completed	Other	Cardiovascular Heart Disease / Prostatic Neoplasms	1
4	Recruiting	Supportive Care	Prostatic Neoplasms	1
4	Suspended	Basic Science	Aging / Menopause / Obesity, Abdominal / Weight Gain	1
4	Terminated	Treatment	Recurrent Prostate Cancer	1
4	Unknown Status	Other	Prostate Cancer	1
3	Active Not Recruiting	Treatment	Prostate Cancer	2
3	Completed	Treatment	Endometriosis	1
3	Completed	Treatment	Infertility / OHSS / Polycystic Ovarian Syndrome	1
3	Completed	Treatment	Prostate Cancer	15

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, for solution		120 mg
Injection, powder, for solution		80 mg
Injection, powder, for solution	Cutaneous; Parenteral	120 MG
Injection, powder, for solution	Cutaneous; Parenteral	80 MG
Injection, powder, for solution	Subcutaneous	120 mg
Injection, powder, for solution	Subcutaneous	80 mg
Powder, for solution	Subcutaneous	120 mg
Powder, for solution	Subcutaneous	80 mg
Powder, metered	Subcutaneous	20 mg/1mL
Powder, metered	Subcutaneous	40 mg/1mL
Injection, powder, lyophilized, for solution	Subcutaneous	120 mg
Injection, powder, lyophilized, for solution	Subcutaneous	80 mg
Powder

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
CA2286190	No	2007-01-09	2018-04-13
US5925730	No	1999-07-20	2021-05-18
US9579359	No	2017-02-28	2029-02-10
US9415085	No	2016-08-16	2032-04-27
US10695398	No	2012-04-27	2032-04-27
US10729739	No	2009-02-10	2029-02-10

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

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0041 mg/mL	ALOGPS
logP	2.66	ALOGPS
logP	0.18	ChemAxon
logS	-5.6	ALOGPS
pKa (Strongest Acidic)	10.55	ChemAxon
pKa (Strongest Basic)	11.16	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	18	ChemAxon
Hydrogen Donor Count	17	ChemAxon
Polar Surface Area	512.87 Å2	ChemAxon
Rotatable Bond Count	41	ChemAxon
Refractivity	431.13 m3·mol-1	ChemAxon
Polarizability	168.98 Å3	ChemAxon
Number of Rings	8	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.8352
Blood Brain Barrier	-	0.953
Caco-2 permeable	-	0.7556
P-glycoprotein substrate	Substrate	0.8461
P-glycoprotein inhibitor I	Non-inhibitor	0.6672
P-glycoprotein inhibitor II	Non-inhibitor	0.7791
Renal organic cation transporter	Non-inhibitor	0.8579
CYP450 2C9 substrate	Non-substrate	0.7299
CYP450 2D6 substrate	Non-substrate	0.8156
CYP450 3A4 substrate	Substrate	0.6482
CYP450 1A2 substrate	Non-inhibitor	0.8566
CYP450 2C9 inhibitor	Non-inhibitor	0.6493
CYP450 2D6 inhibitor	Non-inhibitor	0.8566
CYP450 2C19 inhibitor	Non-inhibitor	0.7291
CYP450 3A4 inhibitor	Non-inhibitor	0.5961
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.8478
Ames test	Non AMES toxic	0.652
Carcinogenicity	Non-carcinogens	0.7848
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.7005 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.8534
hERG inhibition (predictor II)	Inhibitor	0.5235

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

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Drug created on May 06, 2010 10:15 / Updated on October 21, 2020 01:55