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

Molecular Formula	C70H92ClN17O14
Molecular Weight	1431.038
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	10 / 10
E/Z Centers	3
Optical Activity	UNSPECIFIED

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
Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men.	1999	10077358
[Research on synthetic peptides of biological interest].	2001	11769093
Gonadotrophin-releasing hormone antagonists for assisted conception.	2001	11687120
The lung as a route for systemic delivery of therapeutic proteins and peptides.	2001	11686885
Luteinizing hormone-releasing hormone antagonists in prostate cancer.	2001 Aug	11502441
Stimulation effect of galanin-like peptide (GALP) on luteinizing hormone-releasing hormone-mediated luteinizing hormone (LH) secretion in male rats.	2001 Aug	11459819
[GnRH antagonist].	2001 Jan	11235152
Stability of several LHRH antagonists against proteolytic enzymes and identification of degradation products by mass spectrometry.	2001 Jan	11210667
Comparison of agonistic flare-up-protocol and antagonistic multiple dose protocol in ovarian stimulation of poor responders: results of a prospective randomized trial.	2001 May	11331630
Autoregulation of the gonadotropin-releasing hormone (GnRH) system during puberty: effects of antagonistic versus agonistic GnRH analogs in a female rat model.	2001 May	11312152
LHRH antagonist decreases LH and progesterone secretion but does not alter length of estrous cycle in heifers.	2001 Nov	11768120
Comparison of luteal phase profile in gonadotrophin stimulated cycles with or without a gonadotrophin-releasing hormone antagonist.	2001 Nov	11679500
Gonadal pathologies in transgenic mice expressing the rat inhibin alpha-subunit.	2001 Nov	11606469
Use of gonadotrophin releasing hormone (GnRH) antagonist (cetrotide) during ovarian stimulation for in-vitro fertilization treatment: multiple doses and single dose.	2001 Oct	11776508
The role of gonadotropin-releasing hormone antagonists in in vitro fertilization.	2001 Sep	11679902
Use of third generation gonadotropin-releasing hormone antagonists in in vitro fertilization-embryo transfer: a review.	2001 Sep	11524623
Inhibition of growth of ES-2 human ovarian cancers by bombesin antagonist RC-3095, and luteinizing hormone-releasing hormone antagonist Cetrorelix.	2001 Sep 28	11485826
GnRH agonists and antagonists stimulate recovery of fertility in irradiated LBNF1 rats.	2001 Sep-Oct	11545294
[LH and GnRH antagonists].	2002 Apr	11981488
Expression of receptors for luteinizing hormone-releasing hormone in human ovarian and endometrial cancers: frequency, autoregulation, and correlation with direct antiproliferative activity of luteinizing hormone-releasing hormone analogues.	2002 Feb	11854630
New drugs 2002, part 1.	2002 Jan	12352750
Annexin 5 messenger ribonucleic acid expression in pituitary gonadotropes is induced by gonadotropin-releasing hormone (GnRH) and modulates GnRH stimulation of gonadotropin release.	2002 Jan	11810030
Impact of aromatic residues within transmembrane helix 6 of the human gonadotropin-releasing hormone receptor upon agonist and antagonist binding.	2002 Jan 29	11802711
Comparison of cryopreservation outcome with gonadotropin-releasing hormone agonists or antagonists in the collecting cycle.	2002 Mar	11872197
Regulation of microsomal P450, redox partner proteins, and steroidogenesis in the developing testes of the neonatal pig.	2002 Sep	12193548
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
[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
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
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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:32:31 GMT 2023` Edited by `admin` on `Fri Dec 15 15:32:31 GMT 2023`
Record UNII	OON1HFZ4BA
Record Status	`Validated (UNII)`
Record Version

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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