Identification

Name
Abarelix
Accession Number
DB00106  (BTD00051, BIOD00051)
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

Synthetic decapeptide antagonist to gonadotropin releasing hormone (GnRH). It is marketed by Praecis Pharmaceuticals as Plenaxis. Praecis announced in June 2006 that it was voluntarily withdrawing the drug from the market.

Structure
Thumb
Synonyms
Not Available
International/Other Brands
Plenaxis (Praecis Pharmaceuticals)
Categories
UNII
W486SJ5824
CAS number
183552-38-7
Weight
Average: 1416.09
Monoisotopic: 1414.6840715
Chemical Formula
C72H95ClN14O14
InChI Key
AIWRTTMUVOZGPW-HSPKUQOVSA-N
InChI
InChI=1S/C72H95ClN14O14/c1-41(2)32-54(64(93)80-53(17-10-11-30-77-42(3)4)72(101)87-31-13-18-60(87)69(98)78-43(5)63(75)92)81-68(97)58(38-62(74)91)84-70(99)61(37-46-22-27-52(90)28-23-46)86(7)71(100)59(40-88)85-67(96)57(36-48-14-12-29-76-39-48)83-66(95)56(34-45-20-25-51(73)26-21-45)82-65(94)55(79-44(6)89)35-47-19-24-49-15-8-9-16-50(49)33-47/h8-9,12,14-16,19-29,33,39,41-43,53-61,77,88,90H,10-11,13,17-18,30-32,34-38,40H2,1-7H3,(H2,74,91)(H2,75,92)(H,78,98)(H,79,89)(H,80,93)(H,81,97)(H,82,94)(H,83,95)(H,84,99)(H,85,96)/t43-,53+,54+,55-,56-,57-,58-,59+,60+,61+/m1/s1
IUPAC Name
(2R)-N-[(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]-2-[(2S)-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-hydroxy-N-methylpropanamido]-3-(4-hydroxyphenyl)propanamido]butanediamide
SMILES
CC(C)C[[email protected]](NC(=O)[[email protected]@H](CC(N)=O)NC(=O)[[email protected]](CC1=CC=C(O)C=C1)N(C)C(=O)[[email protected]](CO)NC(=O)[[email protected]@H](CC1=CN=CC=C1)NC(=O)[[email protected]@H](CC1=CC=C(Cl)C=C1)NC(=O)[[email protected]@H](CC1=CC2=C(C=CC=C2)C=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

Pharmacology

Indication

For palliative treatment of advanced prostate cancer.

Structured Indications
Not Available
Pharmacodynamics

Used in the palliative treatment of advanced prostate cancer. Abarelix is a luteinizing hormone agonist that results in suppression of testicular or follicular steroidogenesis.

Mechanism of action

Abarelix binds to the gonadotropin releasing hormone receptor and acts as a potent inhibitor of gonadotropin secretion.

TargetActionsOrganism
AGonadotropin-releasing hormone receptor
antagonist
Human
Absorption

Following IM administration of 100 mg, abarelix is absorbed slowly with a mean peak concentration of 43.4 ng/mL observed approximately 3 days after the injection.

Volume of distribution
Not Available
Protein binding

96-99%

Metabolism

In vitro hepatocyte (rat, monkey, human) studies and in vivo studies in rats and monkeys showed that the major metabolites of abarelix were formed via hydrolysis of peptide bonds. No significant oxidative or conjugated metabolites of abarelix were found either in vitro or in vivo. There is no evidence of cytochrome P-450 involvement in the metabolism of abarelix.

Route of elimination
Not Available
Half life

13.2 ± 3.2 days

Clearance
Not Available
Toxicity

The maximum tolerated dose of abarelix has not been determined. The maximum dose used in clinical studies was 150 mg. There have been no reports of accidental overdose with abarelix.

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

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D02738
PubChem Compound
16131215
PubChem Substance
46508237
ChemSpider
10482301
BindingDB
50102442
ChEBI
337298
ChEMBL
CHEMBL1252
Therapeutic Targets Database
DAP000094
PharmGKB
PA164754915
IUPHAR
1188
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Abarelix
ATC Codes
L02BX01 — Abarelix
FDA label
Download (121 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentProstate Cancer1
3CompletedTreatmentProstate Cancer1
4SuspendedTreatmentProstate Cancer1

Pharmacoeconomics

Manufacturers
  • Speciality european pharma ltd
Packagers
Dosage forms
Not Available
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6423686No1995-06-072015-06-07Us
US6180608No1996-12-112016-12-11Us
US5968895No1996-12-112016-12-11Us
US5843901No1995-12-012015-12-01Us
US6699833No1996-12-112016-12-11Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00371 mg/mLALOGPS
logP2.84ALOGPS
logP-0.46ChemAxon
logS-5.6ALOGPS
pKa (Strongest Acidic)9.47ChemAxon
pKa (Strongest Basic)10.66ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count16ChemAxon
Hydrogen Donor Count13ChemAxon
Polar Surface Area424.98 Å2ChemAxon
Rotatable Bond Count38ChemAxon
Refractivity373.91 m3·mol-1ChemAxon
Polarizability149.31 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
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Tyrosine and derivatives / Phenylalanine and derivatives / Asparagine 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 / Amphetamines and derivatives
show 21 more
Substituents
Alpha-oligopeptide / Tyrosine or derivatives / Phenylalanine or derivatives / Asparagine or derivatives / Leucine or derivatives / N-acyl-alpha amino acid or derivatives / Proline or derivatives / Alpha-amino acid amide / Serine or derivatives / Alanine or derivatives
show 45 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
polypeptide (CHEBI:337298)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. Debruyne FM: Gonadotropin-releasing hormone antagonist in the management of prostate cancer. Rev Urol. 2004;6 Suppl 7:S25-32. [PubMed:16985933]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 14:24