CETRORELIX

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C70H92ClN17O14
Molecular Weight	1431.038
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@H](NC(=O)[C@@H](CCCNC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC2=CN=CC=C2)NC(=O)[C@@H](CC3=CC=C(Cl)C=C3)NC(=O)[C@@H](CC4=CC5=CC=CC=C5C=C4)NC(C)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N6CCC[C@H]6C(=O)N[C@H](C)C(N)=O

InChI

InChIKey=SBNPWPIBESPSIF-MHWMIDJBSA-N

InChI=1S/C70H92ClN17O14/c1-39(2)31-52(61(94)82-51(15-9-28-77-69(73)74)68(101)88-30-10-16-58(88)67(100)79-40(3)59(72)92)83-60(93)50(14-8-29-78-70(75)102)81-63(96)54(34-43-20-25-49(91)26-21-43)86-66(99)57(38-89)87-65(98)56(36-45-11-7-27-76-37-45)85-64(97)55(33-42-18-23-48(71)24-19-42)84-62(95)53(80-41(4)90)35-44-17-22-46-12-5-6-13-47(46)32-44/h5-7,11-13,17-27,32,37,39-40,50-58,89,91H,8-10,14-16,28-31,33-36,38H2,1-4H3,(H2,72,92)(H,79,100)(H,80,90)(H,81,96)(H,82,94)(H,83,93)(H,84,95)(H,85,97)(H,86,99)(H,87,98)(H4,73,74,77)(H3,75,78,102)/t40-,50-,51+,52+,53-,54+,55-,56-,57+,58+/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021197s010lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB00050

Cetrorelix is a synthetic decapeptide with gonadotropin-releasing hormone (GnRH) antagonistic activity. GnRH induces the production and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the gonadotrophic cells of the anterior pituitary. Due to a positive estradiol (E2) feedback at midcycle, GnRH liberation is enhanced resulting in an LH-surge. This LH-surge induces the ovulation of the dominant follicle, resumption of oocyte meiosis and subsequently luteinization as indicated by rising progesterone levels. Cetrorelix competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner. Cetrorelix binds to the gonadotropin releasing hormone receptor and acts as a potent inhibitor of gonadotropin secretion. It competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner. Cetrorelix is marketed primarily under the brand name Cetrotide. Cetrotide (cetrorelix acetate for injection) is indicated for the inhibition of premature LH surges in women undergoing controlled ovarian stimulation.

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/label/2008/021197s010lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/11462984	Antagonist 2778		1.21 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Female infertility 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021197s010lbl.pdf	Primary		Approved 8429	CETROTIDE Approved Use Cetrotide (cetrorelix acetate for injection) is indicated for the inhibition of premature LH surges in women undergoing controlled ovarian stimulation. Launch Date 2000

C_max

Value	Dose	Analyte	Population
6.42 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	0.25 mg 1 times / day multiple, subcutaneous dose: 0.25 mg route of administration: Subcutaneous experiment type: MULTIPLE co-administered:	CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
4.97 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	0.25 mg single, subcutaneous dose: 0.25 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
28.5 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	3 mg single, subcutaneous dose: 3 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
44.5 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	0.25 mg 1 times / day multiple, subcutaneous dose: 0.25 mg route of administration: Subcutaneous experiment type: MULTIPLE co-administered:	CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
31.4 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	0.25 mg single, subcutaneous dose: 0.25 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
536 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	3 mg single, subcutaneous dose: 3 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
20.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	0.25 mg 1 times / day multiple, subcutaneous dose: 0.25 mg route of administration: Subcutaneous experiment type: MULTIPLE co-administered:	CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	0.25 mg single, subcutaneous dose: 0.25 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
62.8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	3 mg single, subcutaneous dose: 3 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:	CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
14% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/21197lbl.pdf	3 mg single, subcutaneous dose: 3 mg route of administration: Subcutaneous experiment type: SINGLE co-administered:		CETRORELIX plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
5 mg 1 times / day multiple, subcutaneous (starting) Highest studied dose Dose: 5 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26460564	unhealthy, 58.9 ± 8.3 years n = 27 Health Status: unhealthy Condition: Rheumatoid Arthritis Age Group: 58.9 ± 8.3 years Sex: M+F Population Size: 27 Sources: https://pubmed.ncbi.nlm.nih.gov/26460564	Sources: https://pubmed.ncbi.nlm.nih.gov/26460564

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587		inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C8/9 44 CYP2C19 1478 CYP2E1 882 BSEP 402 MRP2 383 MRP3 157 MRP4 204	CYP 270

Drug as perpetrator

Target	Modality	Activity
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP3 207	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2006/P200600012/53019100_21800AMY10090_W100_1.pdf#PAGE=34 Page: (PMDA_W100) 37	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2006/P200600012/53019100_21800AMY10090_W100_1.pdf#PAGE=34 Page: (PMDA_W100) 37	no
CYP2C8/9 44	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2006/P200600012/53019100_21800AMY10090_W100_1.pdf#PAGE=34 Page: (PMDA_W100) 37	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2006/P200600012/53019100_21800AMY10090_W100_1.pdf#PAGE=34 Page: (PMDA_W100) 37	no
CYP2E1 970	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2006/P200600012/53019100_21800AMY10090_W100_1.pdf#PAGE=34 Page: (PMDA_W100) 37	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2006/P200600012/53019100_21800AMY10090_W100_1.pdf#PAGE=34 Page: (PMDA_W100) 37	no
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	yes [IC50 1.47 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-197_Cetrotide_biopharmr.pdf#page=9 Page: 9.0	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:59224	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:59224
ChemicalBook	CB0316370	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0316370
ChemicalBook	CB9874701	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9874701
MolPort	MolPort-009-194-176	https://www.molport.com/shop/molecule-link/MolPort-009-194-176
MolPort	MolPort-042-652-596	https://www.molport.com/shop/molecule-link/MolPort-042-652-596

PubMed

Title	Date	PubMed
[GnRH antagonists in IVF].	2001 Nov	11917361
The place of gonadotrophin-releasing hormone antagonists in reproductive medicine.	2002	12470569
[Reproductive health--new hormonal agents to treat infertility].	2002	12412351
[LH and GnRH antagonists].	2002 Apr	11981488
The effects of gonadotropin-releasing hormone (GnRH) I and GnRH II on the urokinase-type plasminogen activator/plasminogen activator inhibitor system in human extravillous cytotrophoblasts in vitro.	2002 Dec	12466358
New drugs 2002, part 1.	2002 Jan	12352750
Use of GnRH antagonists in the treatment of endometriosis.	2002 Jul-Aug	12470539
Comparison of the effects of two GnRH antagonists on LH and FSH secretion, follicular growth and ovulation in the mare.	2002 May-Jun	12405453
Tailoring the GnRH antagonist cetrorelix acetate to individual patients' needs in ovarian stimulation for IVF: results of a prospective, randomized study.	2002 Nov	12407036
Effective treatment of experimental ES-2 human ovarian cancers with a cytotoxic analog of luteinizing hormone-releasing hormone AN-207.	2002 Oct	12394258
[Use of GnRH antagonists (cetrorelix) in assisted reproduction: first report in Mexican literature].	2002 Sep	12448050
Inhibition of recovery of spermatogenesis in irradiated rats by different androgens.	2002 Sep	12193551
Regulation of microsomal P450, redox partner proteins, and steroidogenesis in the developing testes of the neonatal pig.	2002 Sep	12193548
Clomiphene-induced LH surges and cetrorelix.	2002 Sep-Oct	12419033
The use of gonadotropin-releasing hormone antagonist in a flexible protocol: a pilot study.	2003 Aug	14520215
Differential effects of gonadotropin-releasing hormone I and II on the urokinase-type plasminogen activator/plasminogen activator inhibitor system in human decidual stromal cells in vitro.	2003 Aug	12915673
Prolactin inhibits annexin 5 expression and apoptosis in the corpus luteum of pseudopregnant rats: involvement of local gonadotropin-releasing hormone.	2003 Aug	12865345
Signalling and anti-proliferative effects mediated by gonadotrophin-releasing hormone receptors after expression in prostate cancer cells using recombinant adenovirus.	2003 Feb	12553876
The use of clomiphene citrate/human menopausal gonadotrophins in conjunction with GnRH antagonist in an IVF/ICSI program is not a cost effective protocol.	2003 Jan	12580839
Ovarian stimulation by clomiphene citrate and hMG in combination with cetrorelix acetate for ICSI cycles.	2003 Jan	12525439
An evaluation of the multiple dose protocol of cetrorelix in single ovary women.	2003 Jan-Feb	12655797
Gonadotrophin-releasing hormone antagonists: will they replace the agonists?	2003 Jan-Feb	12626142
The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.	2003 Jul	12843197
An overview of GnRH antagonists in infertility treatments. Introduction.	2003 Jul	12831912
Actions of GnRH antagonists on IGF-II, IGF-binding protein-2 and pregnancy-associated plasma protein-A in human granulosa-lutein cells.	2003 Jul	12824863
PT-141: a melanocortin agonist for the treatment of sexual dysfunction.	2003 Jun	12851303
Josef Rudinger Memorial Lecture 2002. Peptide related drug research.	2003 Jun	12846479
No influence of body weight on pregnancy rate in patients treated with cetrorelix according to the single- and multiple-dose protocols.	2003 Jun	12831598
Single dose application of cetrorelix in combination with clomiphene for friendly IVF: results of a feasibility study.	2003 Jun	12831591
Safety and efficacy of a 3 mg dose of the GnRH antagonist cetrorelix in preventing premature LH surges: report of two large multicentre, multinational, phase IIIb clinical experiences.	2003 Jun	12831588
The impact of LH serum concentration on the clinical outcome of IVF cycles in patients receiving two regimens of clomiphene citrate/gonadotrophin/0.25 mg cetrorelix.	2003 Jun	12831586
Impact of the gonadotropin-releasing hormone antagonist in oocyte donation cycles.	2003 Jun	12798903
GnRH antagonists in the treatment of gynecological and breast cancers.	2003 Jun	12790790
The administration of the GnRH antagonist, cetrorelix, to ooctye donors simplifies oocyte donation.	2003 Jun	12773455
Pharmacokinetic/pharmacodynamic modeling of luteinizing hormone (LH) suppression and LH surge delay by cetrorelix after single and multiple doses in healthy premenopausal women.	2003 Mar	12638392
Sperm to zona pellucida binding depends on the use of a gonadotropin-releasing hormone agonist or a gonadotropin-releasing hormone antagonist.	2003 Mar	12620461
Stimulation of luteinizing hormone secretion by N-methyl-D,L-aspartic acid in the adult male guinea-pig: incomplete blockade by gonadotropin-releasing hormone receptor antagonism.	2003 May	12694377
Gonadotropin-releasing hormone receptor gene expression during pubertal development of male rats.	2003 May	12606421
[Revisiting the clomifene-gonadotropin protocol in IVF with the use of a GnRH antagonist].	2003 Nov	14623556
Gonadal protection from radiation by GnRH antagonist or recombinant human FSH: a controlled trial in a male nonhuman primate (Macaca fascicularis).	2003 Nov	14596670
Preferential ligand selectivity of the monkey type-II gonadotropin-releasing hormone (GnRH) receptor for GnRH-2 and its analogs.	2003 Nov 14	14604814
GnRH antagonist in in vitro fertilization: where we are now.	2003 Oct	14581880
Regulatory effects of gonadotropin-releasing hormone (GnRH) I and GnRH II on the levels of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinases-1 in primary cultures of human extravillous cytotrophoblasts.	2003 Oct	14557455
GnRH-II analogs for selective activation and inhibition of non-mammalian and type-II mammalian GnRH receptors.	2003 Oct 31	14651258
Role of gonadotropin-releasing hormone (GnRH) in ovarian cancer.	2003 Oct 7	14594454
Depot GnRH agonist versus the single dose GnRH antagonist regimen (cetrorelix, 3 mg) in patients undergoing assisted reproduction treatment.	2003 Sep	14567887
Phase II study of cetrorelix, a luteinizing hormone-releasing hormone antagonist in patients with platinum-resistant ovarian cancer.	2003 Sep	13678723
Gonadotropin-releasing hormone receptor gene expression during pubertal development of female rats.	2004 Feb	14561652
Pituitary and gonadal effects of GnRH (gonadotropin releasing hormone) analogues in two peripubertal female rat models.	2004 Jan	14605254
Expression and function of gonadotropin-releasing hormone (GnRH) receptor in human olfactory GnRH-secreting neurons: an autocrine GnRH loop underlies neuronal migration.	2004 Jan 2	14565958

Patents

Sample Use Guides

In Vivo Use Guide

Ovarian stimulation therapy with gonadotropins (FSH, hMG) is started on cycle Day 2 or 3. The dose of gonadotropins should be adjusted according to individual response. Cetrotide (cetrorelix acetate for injection) may be administered subcutaneously either once daily (0.25 mg dose) or once (3 mg dose) during the early- to mid-follicular phase. In the single dose regimen, 3 mg of Cetrotide (Cetrorelix) is administered when the serum estradiol level is indicative of an appropriate stimulation response, usually on stimulation day 7 (range day 5-9). If hCG has not been administered within four days after injection of Cetrotide 3 mg, Cetrotide 0.25 mg should be administered once daily until the day of hCG administration. In the multiple dose regimen, 0.25 mg of Cetrotide is administered on either stimulation day 5 (morning or evening) or day 6 (morning) and continued daily until the day of hCG administration.

Route of Administration: Other

In Vitro Use Guide

Cetrorelix inhibited rat granulosa cell growth dose-dependently in the range of 10(-10)-10(-5) M

Name

Type

Language

CETRORELIX

Official Name

English

N-ACETYL-3-(2-NAPHTHYL)-D-ALANYL-P-CHLORO-D-PHENYLALANYL-3-(3-PYRIDYL)-D-ALANYL-L-SERYL-L-TYROSYL-N(SUP 5)-CARBAMOYL-D-ORNITHYL-L-LEUCYL-L-ARGINYL-L-PROLYL-D-ALANINAMIDE

Common Name

English

CETRORELIX [VANDF]

Common Name

English

CETRORELIX [EMA EPAR]

Common Name

English

Cetrorelix [WHO-DD]

Common Name

English

CETRORELIX [ORANGE BOOK]

Common Name

English

CETRORELIX [MI]

Common Name

English

CETRORELIX [HSDB]

Common Name

English

cetrorelix [INN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175839