Details of the Drug

General Information of Drug (ID: DMFD9Q6)

Drug Name
Cetrorelix
Synonyms
Cetrorelixum; Cetrorelix (INN); Cetrotide (TN); HS-2008; Ac-D-Nal(2)-D-Phe(pCl)-D-Pal(3)-Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH2; N-acetyl-3-(2-naphthyl)-D-alanyl-4-chloro-D-phenylalanyl-3-(3-pyridyl)-D-alanyl-L-seryl-L-tyrosyl-N5-carbomoyl-D-ornithyl-L-leucyl-L-prolyl-D-alaninamide; N-acetyl-3-(naphthalen-2-yl)-D-alanyl-4-chloro-D-phenylalanyl-3-(pyridin-3-yl)-D-alanyl-L-seryl-L-tyrosyl-N(5)-carbamoyl-D-ornithyl-L-leucyl-L-arginyl-L-prolyl-D-alaninamide
Indication
Disease Entry ICD 11 Status REF
Ovarian stimulation LB45.1 Approved [1], [2]
Therapeutic Class
Infertility Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 4 Molecular Weight (mw) 1431
Topological Polar Surface Area (xlogp) 1.9
Rotatable Bond Count (rotbonds) 38
Hydrogen Bond Donor Count (hbonddonor) 16
Hydrogen Bond Acceptor Count (hbondacc) 16
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Bioavailability
The bioavailability of drug is 85%s [4]
Clearance
The drug present in the plasma can be removed from the body at the rate of 1.2 mL/min/kg [5]
Elimination
3% of drug is excreted from urine in the unchanged form [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 62.8 hours [5]
Metabolism
The drug is metabolized via peptidases [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.14% [5]
Vd
The volume of distribution (Vd) of drug is 1.16 L/kg [6]
Water Solubility
The ability of drug to dissolve in water is measured as 8 mg/mL [3]
Chemical Identifiers
Formula
C70H92ClN17O14
IUPAC Name
(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(carbamoylamino)pentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]-N-[(2R)-1-amino-1-oxopropan-2-yl]pyrrolidine-2-carboxamide
Canonical SMILES
C[C@H](C(=O)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CCCNC(=O)N)NC(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC3=CN=CC=C3)NC(=O)[C@@H](CC4=CC=C(C=C4)Cl)NC(=O)[C@@H](CC5=CC6=CC=CC=C6C=C5)NC(=O)C
InChI
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
InChIKey
SBNPWPIBESPSIF-MHWMIDJBSA-N
Cross-matching ID
PubChem CID
25074887
ChEBI ID
CHEBI:59224
CAS Number
120287-85-6
DrugBank ID
DB00050
TTD ID
D09OLZ

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Gonadotropin-releasing hormone receptor (GNRHR) TT8R70G GNRHR_HUMAN Antagonist [7], [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1190).
2 New drugs in development for the treatment of endometriosis. Expert Opin Investig Drugs. 2008 Aug;17(8):1187-202.
3 BDDCS applied to over 900 drugs
4 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
7 Gonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas. Prostate. 2009 Jul 1;69(10):1025-33.
8 Gonadotrophin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev. 2006 Jul 19;3:CD001750.
9 Use of cognitive behavior therapy for functional hypothalamic amenorrhea. Ann N Y Acad Sci. 2006 Dec;1092:114-29.
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
11 Age attenuates testosterone secretion driven by amplitude-varying pulses of recombinant human luteinizing hormone during acute gonadotrope inhibiti... J Clin Endocrinol Metab. 2007 Sep;92(9):3626-32.
12 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
13 Regulation of GnRH I receptor gene expression by the GnRH agonist triptorelin, estradiol, and progesterone in the gonadotroph-derived cell line alphaT3-1. Endocrine. 2006 Aug;30(1):139-44.
14 Clinical pipeline report, company report or official report of Takeda (2009).
15 Reversible downregulation of endocrine and germinative testicular function (hormonal castration) in the dog with the GnRH-agonist azagly-nafarelin ... Theriogenology. 2009 Apr 15;71(7):1037-45.
16 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
17 Iterative approach to the discovery of novel degarelix analogues: substitutions at positions 3, 7, and 8. Part II. J Med Chem. 2005 Jul 28;48(15):4851-60.
18 Stability of cytotoxic luteinizing hormone-releasing hormone conjugate (AN-152) containing doxorubicin 14-O-hemiglutarate in mouse and human serum in vitro: implications for the design of preclinicalstudies. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):829-34.