Cetrorelix free base | CAS#145672-81-7 | GnRH antagonist

MedKoo Cat#: 461847 | Name: Cetrorelix free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Cetrorelix is is a gonadotropin-releasing hormone (GnRH) antagonist that is marketed primarily under the brand name Cetrotide. A synthetic decapeptide, it is used is used in assisted reproduction to inhibit premature luteinizing hormone surges. The drug works by blocking the action of GnRH upon the pituitary, thus rapidly suppressing the production and action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

Chemical Structure

Cetrorelix free base

CAS#120287-85-6 (free base)

Theoretical Analysis

MedKoo Cat#: 461847

Name: Cetrorelix free base

CAS#: 120287-85-6 (free base)

Chemical Formula: C70H92ClN17O14

Exact Mass: 1429.6698

Molecular Weight: 1431.06

Elemental Analysis: C, 58.75; H, 6.48; Cl, 2.48; N, 16.64; O, 15.65

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Related CAS #

120287-85-6 (free base) 130143-01-0 (2 acetate) 130289-71-3 (3TFA) 145672-81-7 (1 acetate); 165186-69-6 (pamoate)

Synonym

Cetrorelix acetate; Cetrorelix; Cetrotide; D 20761; D-20761; D20761; NS-75A; NS 75A; SB-075 acetate;

IUPAC/Chemical Name

(S)-1-(((R)-2-((S)-2-((S)-2-((R)-2-((R)-2-((R)-2-acetamido-3-(naphthalen-2-yl)propanamido)-3-(4-chlorophenyl)propanamido)-3-(pyridin-3-yl)propanamido)-3-hydroxypropanamido)-3-(4-hydroxyphenyl)propanamido)-5-ureidopentanoyl)-L-leucyl-L-arginyl)-N-((R)-1-amino-1-oxopropan-2-yl)pyrrolidine-2-carboxamide

InChi Key

SBNPWPIBESPSIF-MHWMIDJBSA-N

InChi Code

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

SMILES Code

C[C@@H](NC([C@H]1N(CCC1)C([C@@H](NC([C@@H](NC([C@H](NC([C@@H](NC([C@@H](NC([C@H](NC([C@H](NC([C@H](NC(C)=O)CC2=CC=C3C=CC=CC3=C2)=O)CC4=CC=C(C=C4)Cl)=O)CC5=CC=CN=C5)=O)CO)=O)CC6=CC=C(C=C6)O)=O)CCCNC(N)=O)=O)CC(C)C)=O)CCCNC(N)=N)=O)=O)C(N)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.03.00

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Cetrorelix Acetate (SB-75 acetate) is a potent gonadotropin-releasing hormone (GnRH) receptor antagonist with an IC50 of 1.21 nM.

In vitro activity:

To investigate the effect of LHRH-I antagonist on myeloma cell growth, Cetrorelix was used to treat 8 MM cells lines, including the RPMI 8226–derived ATO- or BZM-resistant cells, and KAS-6/1–derived, lenalidomide-resistant myeloma cells generated in our laboratories. Cetrorelix treatment reduced cell growth after 48 hours in all cell lines. At the concentration of 1 to 2 μmol/L (a concentration comparable with the previous studies; ref. 16), a 20% to 50% decrease of cell growth as compared with the vehicle was seen and a maximal response was reached at 4 μmol/L (Fig. 2A). Importantly, although RPMI 8226-ATOR cells, RPMI 8226-BZMR, and KAS-6/R10R cells show resistance to ATO, BZM, and lenalidomide, respectively (Fig. 2A inset), they remained sensitive to Cetrorelix treatment. The growth inhibition was further confirmed by colony formation assays (Fig. 2B), showing that Cetrorelix (1 μmol/L) reduced colony-forming ability of the two MM cell lines tested. Reference: Mol Cancer Ther. 2011 Jan;10(1):148-58. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=21062912

In vivo activity:

In mice, ovarian stimulation via hormone administration is an effective method for obtaining many ova simultaneously, but its effect is reduced by the influence of aging. In this study, it’s demonstrate that this problem can be improved by administering the gonadotropin-releasing hormone antagonist Cetrorelix prior to ovarian stimulation. Before 12-month-old female mice were injected with 5 IU pregnant mare serum gonadotropin and 5 IU human chorionic gonadotropin, we administered 5 µg/kg Cetrorelix for 7 consecutive days (7 times) or 3 times once every 3 days. As a result, 8.7 ± 1.9 (mean ± SEM, n=10) and 9.8 ± 1.3 (n=10) oocytes were obtained, respectively, as opposed to 4.7 ± 1.2 oocytes (n=9) in the case of no administration. Collagen staining of ovarian tissue showed that Cetrorelix administration reduced the degree of fibrosis, which improved ovarian function. In addition, equivalent fertilization and fetal development rates between control and Cetrorelix-treated aged mouse-derived oocytes were confirmed by in vitro fertilization and embryo transfer (Fertilization rate; control: 92.2% vs. 3 times: 96.9%/7 times: 88.5%, Birth rate; control: 56.4% vs. 3 times: 58.3%/7 times: 51.8%), indicating the normality of the obtained oocytes. It is concluded that Cetrorelix improved the effect of superovulation in aged mice without reducing oocyte quality. This procedure will contribute to animal welfare by extending the effective utilization of aged female breeding mice. Reference: Exp Anim. 2021 Feb 6;70(1):31-36. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32863284/

Preparing Stock Solutions

The following data is based on the product molecular weight 1,431.06 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Wen J, Feng Y, Bjorklund CC, Wang M, Orlowski RZ, Shi ZZ, Liao B, O'Hare J, Zu Y, Schally AV, Chang CC. Luteinizing Hormone-Releasing Hormone (LHRH)-I antagonist cetrorelix inhibits myeloma cell growth in vitro and in vivo. Mol Cancer Ther. 2011 Jan;10(1):148-58. doi: 10.1158/1535-7163.MCT-10-0829. Epub 2010 Nov 9. PMID: 21062912. 2. Gründker C, Emons G. Role of gonadotropin-releasing hormone (GnRH) in ovarian cancer. Reprod Biol Endocrinol. 2003 Oct 7;1:65. doi: 10.1186/1477-7827-1-65. PMID: 14594454; PMCID: PMC239893.

In vivo protocol:

1. Kanda A, Nobukiyo A, Sotomaru Y. Effect of Cetrorelix administration on ovarian stimulation in aged mice. Exp Anim. 2021 Feb 6;70(1):31-36. doi: 10.1538/expanim.20-0058. Epub 2020 Aug 31. PMID: 32863284; PMCID: PMC7887618.

1: Hooshfar S, Mortazavi SA, Piryaei M, Ramandi Darzi H, Shahsavari N, Kobarfard F. Development and Validation of a Reversed-phase HPLC Method for Assay of the Decapeptide Cetrorelix Acetate in Bulk and Pharmaceutical Dosage Forms. Iran J Pharm Res. 2014 Winter;13(Suppl):43-50. PubMed PMID: 24711828; PubMed Central PMCID: PMC3977052. 2: Britten JL, Malik M, Levy G, Mendoza M, Catherino WH. Gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate and GnRH antagonist cetrorelix acetate directly inhibit leiomyoma extracellular matrix production. Fertil Steril. 2012 Nov;98(5):1299-307. doi: 10.1016/j.fertnstert.2012.07.1123. Epub 2012 Aug 14. PubMed PMID: 22901846. 3: Erb K, Klipping C, Duijkers I, Pechstein B, Schueler A, Hermann R. Pharmacodynamic effects and plasma pharmacokinetics of single doses of cetrorelix acetate in healthy premenopausal women. Fertil Steril. 2001 Feb;75(2):316-23. PubMed PMID: 11172833. 4: Kåss AS, Førre OT, Fagerland MW, Gulseth HC, Torjesen PA, Hollan I. Short-term treatment with a gonadotropin-releasing hormone antagonist, cetrorelix, in rheumatoid arthritis (AGRA): a randomized, double-blind, placebo-controlled study. Scand J Rheumatol. 2014;43(1):22-7. doi: 10.3109/03009742.2013.825007. Epub 2013 Nov 1. PubMed PMID: 24182325; PubMed Central PMCID: PMC3913106. 5: Check JH, Wilson C, Choe JK, Amui J, Katsoff B. A comparison of pregnancy rates following fresh and frozen embryo transfer according to the use of leuprolide acetate vs ganirelix vs cetrorelix. Clin Exp Obstet Gynecol. 2010;37(2):105-7. PubMed PMID: 21077496. 6: Wilcox J, Potter D, Moore M, Ferrande L, Kelly E; CAP IV Investigator Group. Prospective, randomized trial comparing cetrorelix acetate and ganirelix acetate in a programmed, flexible protocol for premature luteinizing hormone surge prevention in assisted reproductive technologies. Fertil Steril. 2005 Jul;84(1):108-17. PubMed PMID: 16009165. 7: Martínez F, Clua E, Santmartí P, Boada M, Rodriguez I, Coroleu B. Randomized, comparative pilot study of pituitary suppression with depot leuprorelin versus cetrorelix acetate 3 mg in gonadotropin stimulation protocols for oocyte donors. Fertil Steril. 2010 Nov;94(6):2433-6. doi: 10.1016/j.fertnstert.2010.02.059. Epub 2010 Apr 28. PubMed PMID: 20430379. 8: Erb K, Junge K, Pechstein B, Schneider E, Derendorf H, Hermann R. Novel formulations of cetrorelix acetate in healthy men: pharmacodynamic effects and noncompartmental pharmacokinetics. J Clin Pharmacol. 2002 Sep;42(9):995-1001. PubMed PMID: 12211225. 9: Siejka A, Schally AV, Barabutis N. The effect of LHRH antagonist cetrorelix in crossover conditioned media from epithelial (BPH-1) and stromal (WPMY-1) prostate cells. Horm Metab Res. 2014 Jan;46(1):21-6. doi: 10.1055/s-0033-1349127. Epub 2013 Jul 9. PubMed PMID: 23839655. 10: Torres Mde M, Donadio N, Donadio NF, Brandão AC, Heck B. Comparison of embryo implantation in Wistar rats that underwent ovarian stimulation using exogenous gonadotropins associated with cetrorelix acetate or leuprolide acetate. Fertil Steril. 2005 Oct;84 Suppl 2:1235-40. PubMed PMID: 16210016. 11: Hwang JL, Huang LW, Hsieh BC, Tsai YL, Huang SC, Chen CY, Hsieh ML, Chen PH, Lin YH. Ovarian stimulation by clomiphene citrate and hMG in combination with cetrorelix acetate for ICSI cycles. Hum Reprod. 2003 Jan;18(1):45-9. PubMed PMID: 12525439. 12: Ludwig M, Katalinic A, Banz C, Schröder AK, Löning M, Weiss JM, Diedrich K. Tailoring the GnRH antagonist cetrorelix acetate to individual patients' needs in ovarian stimulation for IVF: results of a prospective, randomized study. Hum Reprod. 2002 Nov;17(11):2842-5. PubMed PMID: 12407036. 13: Silva ME, Smulders JP, Guerra M, Valderrama XP, Letelier C, Adams GP, Ratto MH. Cetrorelix suppresses the preovulatory LH surge and ovulation induced by ovulation-inducing factor (OIF) present in llama seminal plasma. Reprod Biol Endocrinol. 2011 May 30;9:74. doi: 10.1186/1477-7827-9-74. PubMed PMID: 21624125; PubMed Central PMCID: PMC3123631. 14: Engel JB, Audebert A, Frydman R, Zivny J, Diedrich K. Presurgical short term treatment of uterine fibroids with different doses of cetrorelix acetate: a double-blind, placebo-controlled multicenter study. Eur J Obstet Gynecol Reprod Biol. 2007 Oct;134(2):225-32. Epub 2006 Aug 22. PubMed PMID: 16930803. 15: Lai Q, Hu J, Zeng D, Hu J, Cai F, Yang F, Chen C, He X, Yang P, Yu Q, Zhang S, Xu JF, Wang CY. Assessing the optimal dose for Cetrorelix in Chinese women undergoing ovarian stimulation during the course of IVF-ET treatment. Am J Transl Res. 2013 Dec 1;6(1):78-84. eCollection 2013. PubMed PMID: 24349624; PubMed Central PMCID: PMC3853427. 16: Hwang JL, Seow KM, Lin YH, Huang LW, Hsieh BC, Tsai YL, Wu GJ, Huang SC, Chen CY, Chen PH, Tzeng CR. Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study. Hum Reprod. 2004 Sep;19(9):1993-2000. Epub 2004 Jul 29. PubMed PMID: 15284212. 17: Yang D, Hou T, Yang X, Ma Y, Wang L, Li B. Mechanisms of prostate atrophy after LHRH antagonist cetrorelix injection: an experimental study in a rat model of benign prostatic hyperplasia. J Huazhong Univ Sci Technolog Med Sci. 2012 Jun;32(3):389-395. doi: 10.1007/s11596-012-0067-x. Epub 2012 Jun 9. PubMed PMID: 22684563. 18: Wen J, Feng Y, Bjorklund CC, Wang M, Orlowski RZ, Shi ZZ, Liao B, O'Hare J, Zu Y, Schally AV, Chang CC. Luteinizing Hormone-Releasing Hormone (LHRH)-I antagonist cetrorelix inhibits myeloma cell growth in vitro and in vivo. Mol Cancer Ther. 2011 Jan;10(1):148-58. doi: 10.1158/1535-7163.MCT-10-0829. Epub 2010 Nov 9. PubMed PMID: 21062912. 19: Sauer MV, Thornton MH 2nd, Schoolcraft W, Frishman GN. Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction. Reprod Biomed Online. 2004 Nov;9(5):487-93. PubMed PMID: 15588464. 20: Chen HJ, Lin YH, Hsieh BC, Seow KM, Hwang JL, Tzeng CR. Is a lower dose of cetrorelix acetate effective for prevention of LH surge during controlled ovarian hyperstimulation? J Assist Reprod Genet. 2006 Jun;23(6):289-92. Epub 2006 Jul 22. PubMed PMID: 16865530; PubMed Central PMCID: PMC3506367.