ABARELIX

US Previously Marketed

First approved in 2003

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C72H95ClN14O14
Molecular Weight	1416.0658
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@@]([H])(C(=N[C@@]([H])(CCCCNC(C)C)C(=O)N1CCC[C@@]1([H])C(=N[C@]([H])(C)C(=N)O)O)O)NN[C@]([H])(CC(=N)O)C(=O)C(=O)[C@]([H])(Cc2ccc(cc2)O)N(C)C(=O)[C@]([H])(CO)N=C([C@@]([H])(Cc3cccnc3)N=C([C@@]([H])(Cc4ccc(cc4)Cl)N=C([C@@]([H])(Cc5ccc6ccccc6c5)N=C(C)O)O)O)O

InChI

InChIKey=LNNDRFNNTDYHIO-OMYILHBOSA-N

InChI=1S/C72H95ClN14O14/c1-41(2)32-58(69(98)80-53(17-10-11-30-77-42(3)4)72(101)87-31-13-18-60(87)70(99)78-43(5)65(75)94)85-84-54(38-62(74)91)63(92)64(93)61(37-46-22-27-52(90)28-23-46)86(7)71(100)59(40-88)83-68(97)57(36-48-14-12-29-76-39-48)82-67(96)56(34-45-20-25-51(73)26-21-45)81-66(95)55(79-44(6)89)35-47-19-24-49-15-8-9-16-50(49)33-47/h8-9,12,14-16,19-29,33,39,41-43,53-61,77,84-85,88,90H,10-11,13,17-18,30-32,34-38,40H2,1-7H3,(H2,74,91)(H2,75,94)(H,78,99)(H,79,89)(H,80,98)(H,81,95)(H,82,96)(H,83,97)/t43-,53+,54-,55-,56-,57-,58+,59+,60+,61+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB00106
Curator's Comment:: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-320_Plenaxis_Prntlbl.pdf

Abarelix is a synthetic decapeptide antagonist to gonadotropin releasing hormone (GnRH). It is marketed by Praecis Pharmaceuticals as Plenaxis. Used in the palliative treatment of advanced prostate cancer. Abarelix is a luteinizing hormone agonist that results in suppression of testicular or follicular steroidogenesis. Abarelix binds to the gonadotropin releasing hormone receptor and acts as a a potent inhibitor of gonadotropin secretion. Praecis announced in June 2006 that it was voluntarily withdrawing the drug from the market.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gonadotropin-releasing hormone receptor 19 Target ID: CHEMBL1855 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-320_Plenaxis_Prntlbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/16985933	Antagonist 1131		3.5 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced prostate cancer 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-320_Plenaxis_Prntlbl.pdf	Palliative		Approved 4033	Plenaxis Approved Use For palliative treatment of advanced prostate cancer. Launch Date 1.069632E12

C_max

Value	Dose	Co-administered	Analyte	Population
43.4 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21320_plenaxis_lbl.pdf	100 mg single, intramuscular dose: 100 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		ABARELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
500 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21320_plenaxis_lbl.pdf	100 mg single, intramuscular dose: 100 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		ABARELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21320_plenaxis_lbl.pdf	100 mg single, intramuscular dose: 100 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		ABARELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21320_plenaxis_lbl.pdf	100 mg single, intramuscular dose: 100 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		ABARELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
15 ug/kg 1 times / 3 weeks multiple, intramuscular Dose: 15 ug/kg, 1 times / 3 weeks Route: intramuscular Route: multiple Dose: 15 ug/kg, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/	healthy, 50 - 75 years n = 15 Health Status: healthy Age Group: 50 - 75 years Sex: M Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/	Other AEs: Libido decreased... Other AEs: Libido decreased (11 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/
15 ug/kg single, intramuscular Dose: 15 ug/kg Route: intramuscular Route: single Dose: 15 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/	healthy, 50 - 75 years n = 16 Health Status: healthy Age Group: 50 - 75 years Sex: M Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/	Other AEs: Libido decreased... Other AEs: Libido decreased (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/

AEs

AE	Significance	Dose	Population
Libido decreased	11 patient	15 ug/kg 1 times / 3 weeks multiple, intramuscular Dose: 15 ug/kg, 1 times / 3 weeks Route: intramuscular Route: multiple Dose: 15 ug/kg, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/	healthy, 50 - 75 years n = 15 Health Status: healthy Age Group: 50 - 75 years Sex: M Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/
Libido decreased	2 patients	15 ug/kg single, intramuscular Dose: 15 ug/kg Route: intramuscular Route: single Dose: 15 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/	healthy, 50 - 75 years n = 16 Health Status: healthy Age Group: 50 - 75 years Sex: M Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/15102870/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:337298	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:337298
ChemicalBook	CB11117588	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB11117588
MolPort	MolPort-006-167-469	https://www.molport.com/shop/molecule-link/MolPort-006-167-469

PubMed

Title	Date	PubMed
Emerging pharmacologic therapies for prostate cancer.	2001	16986005
The evolution of hormonal therapy for prostatic carcinoma.	2001	16986002
Androgen deprivation and other treatments for advanced prostate cancer.	2001	16986000
The gonadotropin-releasing hormone antagonist abarelix depot versus luteinizing hormone releasing hormone agonists leuprolide or goserelin: initial results of endocrinological and biochemical efficacies in patients with prostate cancer.	2001 May	11342922
New single-isomer compounds on the horizon.	2002 Apr	15131493
A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer.	2002 Apr	11912385
Hormonal therapy of prostate cancer.	2002 Aug	12198632
Gateways to clinical trials.	2002 Nov	12616707
Abarelix: abarelix-depot-F, abarelix-depot-M, abarelix-L, PPI 149, R 3827.	2003	12757402
Encouraging results for Plenaxis in prostate cancer trial.	2003 Apr	12722871
Pharmacokinetics and pharmacodynamics of abarelix, a gonadotropin-releasing hormone antagonist, after subcutaneous continuous infusion in patients with prostate cancer.	2003 Apr	12709720
Luteinizing hormone-releasing hormone agonists in the treatment of men with prostate cancer: timing, alternatives, and the 1-year implant.	2003 Dec 22	14706507
Phase II study of abarelix depot for androgen independent prostate cancer progression during gonadotropin-releasing hormone agonist therapy.	2003 May	12686821
Gateways to clinical trials.	2003 Nov	14685303
An open-label study of abarelix in men with symptomatic prostate cancer at risk of treatment with LHRH agonists.	2003 Nov	14624912
Gonadotropin-releasing hormone antagonist in the management of prostate cancer.	2004	16985933
Abarelix (plenaxis).	2004 Dec	15637961
Plenaxis.	2004 Feb	20705014
Targeting FSH in androgen-independent prostate cancer: abarelix for prostate cancer progressing after orchiectomy.	2004 Feb	14972486
Abarelix (Plenaxis): a gonadotropin-releasing hormone antagonist for medical castration in patients with advanced prostate cancer.	2004 Mar	15072602
Abarelix (Plenaxis) for advanced prostate cancer.	2004 Mar 15	15037857
New treatment for advanced prostate cancer.	2004 Mar-Apr	15101352
Pharmacokinetics and pharmacodynamics of a novel depot formulation of abarelix, a gonadotropin-releasing hormone (GnRH) antagonist, in healthy men ages 50 to 75.	2004 May	15102870
Abarelix: the first gonadotrophin-releasing hormone antagonist for the treatment of prostate cancer.	2004 Oct	15461552
Hormone therapy in prostate cancer: LHRH antagonists versus LHRH analogues.	2004 Sep	15306097
Prostate-specific antigen decline after gonadotropin-releasing hormone antagonist withdrawal in androgen-independent prostate cancer.	2005 Apr	15833548
[GnRH antagonists: present and future].	2005 Oct	16302712
The effect of androgen deprivation therapy on fasting serum lipid and glucose parameters.	2006 Aug	16813881
Discovery of a pituitary adenoma following a gonadotropin-releasing hormone agonist in a patient with prostate cancer.	2006 Mar	16643633
Dose-escalated abarelix in androgen-independent prostate cancer: a phase I study.	2006 Oct	17001181
Proprietary Rel-Ease drug delivery technology: opportunity for sustained delivery of peptides, proteins and small molecules.	2006 Sep	16948561
Hormone ablation therapy: lightening the load for today's prostate cancer patient.	2007 Feb	17474637
Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902.	2007 Feb	17095587
Distinguishing compounds with anticancer activity by ANN using inductive QSAR descriptors.	2008 Jul 30	18841240
Six-month depot formulation of leuprorelin acetate in the treatment of prostate cancer.	2009	19554097
Degarelix and its therapeutic potential in the treatment of prostate cancer.	2009	19503784
Will GnRH antagonists improve prostate cancer treatment?	2009 Jan	19008119
[GnRH antagonists--a new therapy option for advanced prostate cancer].	2009 May	19399720
Retraction statement: Reconstitution of Plenaxis® (Abarelix) 100 mg for injection is more effective with a vortex-like mixer than when performed manually.	2010 Feb	21507797
Degarelix, a novel GnRH antagonist, causes minimal histamine release compared with cetrorelix, abarelix and ganirelix in an ex vivo model of human skin samples.	2010 Oct	20840449

Patents

Sample Use Guides

In Vivo Use Guide

Adults Prostate Cancer IM 100 mg on days 1, 15, and 29 (week 4), and then every 4 weeks thereafter. Administer by IM injection into the buttock.

Route of Administration: Intramuscular

In Vitro Use Guide

At 30 and 300 ug/ml concentrations abarelix (143 ± 29% and 362 ± 58%, respectively, P < 0.05) caused significantly increased histamine release.

Name

Type

Language

ABARELIX

Official Name

English

ABARELIX [WHO-DD]

Common Name

English

ABARELIX [ORANGE BOOK]

Common Name

English

ABARELIX [VANDF]

Common Name

English

R-3827

Code

English

PPI-149

Code

English

R-382

Code

English

R382

Code

English

ABARELIX [INN]

Common Name

English

N-ACETYL-3-(2-NAPHTHYL)-D-ALANYL-4-CHLORO-D-PHENYLALANYL-3-(3-PYRIDYL)-D-ALANYL-L-SERYL-N-METHYL-L-TYROSYL-D-ASPARAGINYL-L-LEUCYL-N(SUP 6)-ISOPROPYL-L-LYSYL-L-PROLYL-D-ALANINAMIDE

Common Name

English

ABARELIX [MART.]

Common Name

English

R3827

Code

English

ABARELIX [USAN]

Common Name

English

PLENAXIS

Brand Name

English

ABARELIX [MI]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QL02BX01