ABARELIX

US Previously Marketed

First approved in 2003

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C72H95ClN14O14
Molecular Weight	1416.063
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@H](NN[C@H](CC(N)=O)C(=O)C(=O)[C@H](CC1=CC=C(O)C=C1)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC2=CC=CN=C2)NC(=O)[C@@H](CC3=CC=C(Cl)C=C3)NC(=O)[C@@H](CC4=CC=C5C=CC=CC5=C4)NC(C)=O)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N6CCC[C@H]6C(=O)N[C@H](C)C(N)=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 41 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 2778		3.5 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced prostate cancer 9 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-320_Plenaxis_Prntlbl.pdf	Palliative		Approved 8429	Plenaxis Approved Use For palliative treatment of advanced prostate cancer. Launch Date 2003

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
The evolution of hormonal therapy for prostatic carcinoma.	2001	16986002
Androgen deprivation and other treatments for advanced prostate cancer.	2001	16986000
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.	2001 Feb 1	11462984
Hormonal therapy of prostate cancer.	2002 Aug	12198632
Gateways to clinical trials.	2002 May	12092009
Gateways to clinical trials.	2002 Nov	12616707
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
Gateways to clinical trials.	2003 Nov	14685303
Gonadotropin-releasing hormone antagonist in the management of prostate cancer.	2004	16985933
Plenaxis.	2004 Feb	20705014
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
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
Discovery of a pituitary adenoma following treatment with a gonadotropin-releasing hormone agonist in a patient with prostate cancer.	2006 Jan	16448441
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
Leuprorelin depot injection: patient considerations in the management of prostatic cancer.	2008 Apr	18728847
Distinguishing compounds with anticancer activity by ANN using inductive QSAR descriptors.	2008 Jul 30	18841240
Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer.	2009 Dec	20053189
GnRH antagonists in the treatment of advanced prostate cancer.	2010 Apr	20398443
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
Evaluation of degarelix in the management of prostate cancer.	2010 Jan 25	21188095

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 [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

Abarelix [WHO-DD]

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