Details of the Drug

General Information of Drug (ID: DMAQ469)

Drug Name

Gonadorelin

Synonyms

Dirigestran; Factrel; Fertagyl; Gonadorelina; Gonadorelinum; Hypocrine; Kryptocur; LFRH; LHFSHRH; Luforan; Luliberin; Lutal; Lutamin; Lutrefact; Relefact; Relisorm; Dirigestran Spofa; Gonadoliberin I; Gonadotropin releasing hormone; LHFSH Releasing Hormone; LUTEINIZING HORMONE; Lutrepulse KIT; MammalianGnRH; Relisorm l; Synthetic LRF; Synthetic gonadoliberin; HOE 471; AY-24031; FSH-Releasing Hormone; Fertagyl (TN); GnRH-I; Gonadorelin (INN); Gonadorelin [INN:BAN]; Gonadorelina [INN-Spanish]; Gonadorelinum [INN-Latin]; Gonadotropin-releasing factor; Gonadotropin-releasing hormone; Gonadotropin-releasing hormone I; Human LH-RH; LH-FSH Releasing Hormone; LH-Releasing hormone; Luteinizing hormone-releasing hormone; Mammalian LH-RH; Mammalian gonadotropin-releasing hormone; Ovine LH-RH; Ovine gonadotropin-releasing hormone; Porchine LH-RH; Porcine LH-releasing factor; Synthetic Gn-RH; Synthetic LH-FSH releasing hormone; Synthetic LH-RF; Synthetic LH-RH; Synthetic LH-releasing factor; Synthetic LH-releasing hormone; Synthetic gonadotropic hormone-releasing hormone; Synthetic gonadotropin-releasing hormone; LH-RH (swine); LH-Releasing factor (pig); LH-Releasing hormone (porcine); Luteinizing hormone-releasing factor (human); Luteinizing hormone-releasing factor (pig); Luteinizing hormone-releasing factor (rat); Luteinizing hormone-releasing factor (sheep); Luteinizing hormone-releasing factor (swine); Luteinizing hormone-releasing hormone (swin); Synthetic LH-FSH-RH; Synthetic decapeptide FSH/LH-RH; Follicle-stimulating hormone-releasing factor (pig); Gonadotropin, luteinizing hormone-releasing hormone, synthetic; Synthetic LH-RH/FSH-RH; Synthetic LH-releasing hormone/FSH-releasing hormone; PyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2

Indication

Disease Entry	ICD 11	Status	REF
Hypothalamic hypogonadism	5A61.2	Approved	[1], [2]

Therapeutic Class

Fertility Agents

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 5

Molecular Weight (mw)

1182.3

Topological Polar Surface Area (xlogp)

-2.4

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is rapidly absorbed when injected [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 2 - 10 minutes [4]
Metabolism: The drug is metabolized via the hydrolyzed to inactive peptide components [3]

Chemical Identifiers

Formula: C55H75N17O13
IUPAC Name: (2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[(2S)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide
Canonical SMILES: CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N)NC(=O)CNC(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=CNC4=CC=CC=C43)NC(=O)[C@H](CC5=CN=CN5)NC(=O)[C@@H]6CCC(=O)N6
InChI: InChI=1S/C55H75N17O13/c1-29(2)19-38(49(80)67-37(9-5-17-60-55(57)58)54(85)72-18-6-10-43(72)53(84)62-25-44(56)75)66-46(77)26-63-47(78)39(20-30-11-13-33(74)14-12-30)68-52(83)42(27-73)71-50(81)40(21-31-23-61-35-8-4-3-7-34(31)35)69-51(82)41(22-32-24-59-28-64-32)70-48(79)36-15-16-45(76)65-36/h3-4,7-8,11-14,23-24,28-29,36-43,61,73-74H,5-6,9-10,15-22,25-27H2,1-2H3,(H2,56,75)(H,59,64)(H,62,84)(H,63,78)(H,65,76)(H,66,77)(H,67,80)(H,68,83)(H,69,82)(H,70,79)(H,71,81)(H4,57,58,60)/t36-,37-,38-,39-,40-,41-,42-,43-/m0/s1
InChIKey: XLXSAKCOAKORKW-AQJXLSMYSA-N

Cross-matching ID

PubChem CID: 638793
ChEBI ID: CHEBI:5520
CAS Number: 9034-40-6
DrugBank ID: DB00644
TTD ID: D04ODH
INTEDE ID: DR1929

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	Agonist	[5]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Metallo-endopeptidase-like 1 (MMEL1)	DEYCUQ2	MMEL1_HUMAN	Substrate	[6]
Prolyl endopeptidase (PREP)	DEVSCNZ	PPCE_HUMAN	Substrate	[7]
Thimet oligopeptidase (THOP1)	DE95LJC	THOP1_HUMAN	Substrate	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

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: 4391).
2	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3	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.
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Use of cognitive behavior therapy for functional hypothalamic amenorrhea. Ann N Y Acad Sci. 2006 Dec;1092:114-29.
6	Cell-specific activity of neprilysin 2 isoforms and enzymic specificity compared with neprilysin. Biochem J. 2002 May 1;363(Pt 3):697-705.
7	Ion-exchange chromatography: basic principles and application to the partial purification of soluble mammalian prolyl oligopeptidase. Methods Mol Biol. 2011;681:215-28.
8	Sleep deprivation changes thimet oligopeptidase (THOP1) expression and activity in rat brain. Heliyon. 2019 Nov 26;5(11):e02896.
9	Bradykinin release and inactivation in brain of rats submitted to an experimental model of Alzheimer's disease. Peptides. 2006 Dec;27(12):3363-9.
10	Expression and activity of thimet oligopeptidase (TOP) are modified in the hippocampus of subjects with temporal lobe epilepsy (TLE). Epilepsia. 2014 May;55(5):754-62.
11	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
12	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.
13	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
14	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.
15	Clinical pipeline report, company report or official report of Takeda (2009).
16	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.
17	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.
18	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
19	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.
20	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.