NAFARELIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C66H83N17O13
Molecular Weight	1322.4739
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@H](NC(=O)[C@@H](CC1=CC2=C(C=CC=C2)C=C1)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CO)NC(=O)[C@H](CC4=CNC5=CC=CC=C45)NC(=O)[C@H](CC6=CNC=N6)NC(=O)[C@@H]7CCC(=O)N7)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N8CCC[C@H]8C(=O)NCC(N)=O

InChI

InChIKey=RWHUEXWOYVBUCI-ITQXDASVSA-N

InChI=1S/C66H83N17O13/c1-36(2)25-48(58(89)76-47(13-7-23-71-66(68)69)65(96)83-24-8-14-54(83)64(95)73-33-55(67)86)77-60(91)50(28-38-15-18-39-9-3-4-10-40(39)26-38)78-59(90)49(27-37-16-19-43(85)20-17-37)79-63(94)53(34-84)82-61(92)51(29-41-31-72-45-12-6-5-11-44(41)45)80-62(93)52(30-42-32-70-35-74-42)81-57(88)46-21-22-56(87)75-46/h3-6,9-12,15-20,26,31-32,35-36,46-54,72,84-85H,7-8,13-14,21-25,27-30,33-34H2,1-2H3,(H2,67,86)(H,70,74)(H,73,95)(H,75,87)(H,76,89)(H,77,91)(H,78,90)(H,79,94)(H,80,93)(H,81,88)(H,82,92)(H4,68,69,71)/t46-,47-,48-,49-,50+,51-,52-,53-,54-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019886s032lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/2140979

Nafarelin acetate (brand name Synarel) is a synthetic agonist of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LH-RH), which is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions and for the treatment of central precocious puberty (CPP). Nafarelin has also been used effectively in in vitro fertilisation programmes, and in hirsute women and those with uterine leiomyoma, particularly to induce preoperative fibroid shrinkage. Side effects are related to the low estrogen state and include hot flashes, vaginal dryness, headaches, mood changes, and decreased interest in sex.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gonadotropin-releasing hormone receptor 41 Target ID: CHEMBL1855 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2137975	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Central precocious puberty 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019886s032lbl.pdf	Primary		Approved 8583	SYNAREL Approved Use FOR CENTRAL PRECOCIOUS PUBERTY (For Endometriosis, See Reverse Side) SYNAREL is indicated for treatment of central precocious puberty (CPP) (gonadotropin-dependent precocious puberty) in children of both sexes. The diagnosis of central precocious puberty (CPP) is suspected when premature development of secondary sexual characteristics occurs at or before the age of 8 years in girls and 9 years in boys, and is accompanied by significant advancement of bone age and/or a poor adult height prediction. The diagnosis should be confirmed by pubertal gonadal sex steroid levels and a pubertal LH response to stimulation by native GnRH. Pelvic ultrasound assessment in girls usually reveals enlarged uterus and ovaries, the latter often with multiple cystic formations. Magnetic resonance imaging or CT-scanning of the brain is recommended to detect hypothalamic or pituitary tumors, or anatomical changes associated with increased intracranial pressure. Other causes of sexual precocity, such as congenital adrenal hyperplasia, testotoxicosis, testicular tumors and/or other autonomous feminizing or masculinizing disorders must be excluded by proper clinical hormonal and diagnostic imaging examinations., INDICATIONS AND USAGE FOR ENDOMETRIOSIS (For Central Precocious Puberty, See Reverse Side) SYNAREL is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions. Experience with SYNAREL for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months. Launch Date 1990
Endometriosis 32 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019886s032lbl.pdf	Primary		Approved 8583	SYNAREL Approved Use FOR CENTRAL PRECOCIOUS PUBERTY (For Endometriosis, See Reverse Side) SYNAREL is indicated for treatment of central precocious puberty (CPP) (gonadotropin-dependent precocious puberty) in children of both sexes. The diagnosis of central precocious puberty (CPP) is suspected when premature development of secondary sexual characteristics occurs at or before the age of 8 years in girls and 9 years in boys, and is accompanied by significant advancement of bone age and/or a poor adult height prediction. The diagnosis should be confirmed by pubertal gonadal sex steroid levels and a pubertal LH response to stimulation by native GnRH. Pelvic ultrasound assessment in girls usually reveals enlarged uterus and ovaries, the latter often with multiple cystic formations. Magnetic resonance imaging or CT-scanning of the brain is recommended to detect hypothalamic or pituitary tumors, or anatomical changes associated with increased intracranial pressure. Other causes of sexual precocity, such as congenital adrenal hyperplasia, testotoxicosis, testicular tumors and/or other autonomous feminizing or masculinizing disorders must be excluded by proper clinical hormonal and diagnostic imaging examinations., INDICATIONS AND USAGE FOR ENDOMETRIOSIS (For Central Precocious Puberty, See Reverse Side) SYNAREL is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions. Experience with SYNAREL for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months. Launch Date 1990

C_max

Value	Dose	Co-administered	Analyte	Population
0.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	84 μg single, nasal dose: 84 μg route of administration: Nasal experiment type: SINGLE co-administered:		NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN
0.35 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	206 μg single, nasal dose: 206 μg route of administration: Nasal experiment type: SINGLE co-administered:		NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN
1.59 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	391 μg single, nasal dose: 391 μg route of administration: Nasal experiment type: SINGLE co-administered:		NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN
13.66 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	400 μg single, subcutaneous dose: 400 μg route of administration: Subcutaneous experiment type: SINGLE co-administered:		NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
4.02 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	304 μg single, nasal dose: 304 μg route of administration: Nasal experiment type: SINGLE co-administered: SODIUM GLYCOCHOLATE	SODIUM GLYCOCHOLATE	NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
0.07 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	84 μg single, nasal dose: 84 μg route of administration: Nasal experiment type: SINGLE co-administered:		NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN
0.58 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	206 μg single, nasal dose: 206 μg route of administration: Nasal experiment type: SINGLE co-administered:		NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN
2.15 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	391 μg single, nasal dose: 391 μg route of administration: Nasal experiment type: SINGLE co-administered:		NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN
49.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	400 μg single, subcutaneous dose: 400 μg route of administration: Subcutaneous experiment type: SINGLE co-administered:		NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	304 μg single, nasal dose: 304 μg route of administration: Nasal experiment type: SINGLE co-administered: SODIUM GLYCOCHOLATE	SODIUM GLYCOCHOLATE	NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	400 μg single, subcutaneous dose: 400 μg route of administration: Subcutaneous experiment type: SINGLE co-administered:		NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN
2.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2970910/	304 μg single, nasal dose: 304 μg route of administration: Nasal experiment type: SINGLE co-administered: SODIUM GLYCOCHOLATE	SODIUM GLYCOCHOLATE	NAFARELIN serum	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 ug 2 times / day multiple, intranasal Highest studied dose Dose: 400 ug, 2 times / day Route: intranasal Route: multiple Dose: 400 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019886s030lbl.pdf	healthy, adult Health Status: healthy Age Group: adult Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019886s030lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019886s030lbl.pdf
600 ug 1 times / day multiple, intranasal Highest studied dose Dose: 600 ug, 1 times / day Route: intranasal Route: multiple Dose: 600 ug, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019886s030lbl.pdf	unhealthy, children Health Status: unhealthy Age Group: children Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019886s030lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019886s030lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	peptidase 3 CYP 303

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 303	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019886s033s035lbl.pdf#page=6 Page: 6.0	no
peptidase 3	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/019886s033s035lbl.pdf#page=6 Page: 6.0	yes

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-0495	http://www.3bsc.com/index/pro_info.php?id=19851
AA Blocks	AA0038ZS	https://www.aablocks.com/goods/Goods/detail?id=AA0038ZS
Aaron Chemicals	AR0039RK	http://www.aaronchem.com/76932-56-4
Achemtek	0101-000391	http://www.achemtek.com/76932-56-4
Acorn PharmaTech	ACN-049488	http://www.acornpharmatech.com/
AHH Chemical co.,ltd	API-1473	http://www.ahhchemical.com/product/API-1473.html
AK Scientific, Inc. (AKSCI)	K335	http://www.aksci.com/item_detail.php?cat=K335
Ambinter	Amb10974869	http://www.ambinter.com/reference/10974869
Aurora Fine Chemicals LLC	A18.033.702	http://online.aurorafinechemicals.com/info?ID=A18.033.702
AvaChem Scientific	2225	http://www.avachem.com/productSearch.asp?2225
BOC Sciences	76932-56-4	https://www.bocsci.com/nafarelin-cas-76932-56-4-item-84-465322.html
ChemMol	49423091	http://www.chemmol.com/chemmol/49423091.html
ChemMol	99145872	http://www.chemmol.com/chemmol/99145872.html
ChemShuttle	141336	http://www.chemshuttle.com/catalogsearch/result/?q=76932-56-4&cat=
Chemspace	CSSB02125553727	https://chem-space.com/CSSB02125553727
CSNpharm	CSN11509	https://www.csnpharm.com/products/nafarelin.html
eNovation Chemicals	D680245	https://www.enovationchem.com/ProductDetails.asp?ProductID=D680245
Glentham Life Sciences	GP2823	http://www.glentham.com/products/product/GP2823/
Hairui	HR124775	http://www.hairuichem.com/en/product/76932-56-4.html
Lab Network	LN01805851	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01805851
MolPort	MolPort-006-823-890	https://www.molport.com/shop/molecule-link/MolPort-006-823-890
MuseChem	I004836	https://www.musechem.com/product/I004836.html
OChem	9370	http://www.ocheminc.com/index.php?act=psearch&pid=932N564
Smolecule	S536593	http://www.smolecule.com/products/s536593
THE BioTek	bt-275918	https://www.thebiotek.com/product/inhibitors/bt-275918
Tocris	2544	https://www.tocris.com/products/nafarelin_2544

PubMed

Title	Date	PubMed
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942

Patents

Sample Use Guides

In Vivo Use Guide

For the treatment of central precocious puberty (CPP), the recommended daily dose is 1600 µg. The dose can be increased to 1800 µg daily if adequate suppression cannot be achieved at 1600 µg/day. The 1600 µg dose is achieved by two sprays (400 µg) into each nostril in the morning (4 sprays) and two sprays into each nostril in the evening (4 sprays), a total of 8 sprays per day. The 1800 µg dose is achieved by 3 sprays (600 µg) into alternating nostrils three times a day, a total of 9 sprays per day. The patient’s head should be tilted back slightly, and 30 seconds should elapse between sprays.

Route of Administration: Nasal

In Vitro Use Guide

The binding of LHRH and [6-(3-(2-naphthyl)-D-Ala]LHRH (nafarelin acetate), a highly potent LHRH agonist, to plasma proteins was investigated in vitro by equilibrium dialysis at 4 degrees C with fresh plasma from normal human subjects, female rhesus monkeys, and female rats. Over a wide range of concentrations (10(-8) to 10(-5) M), 78-84% of nafarelin acetate and only 22-25% of LHRH were bound to undiluted plasma. With 10% plasma, the extent of binding was 31-37%, and 0.9-4.2% for nafarelin acetate and LHRH, respectively.

Name

Type

Language

NAFARELIN

Official Name

English

5-OXOPRO-HIS-TRP-SER-TYR-D-NAL(2)-LEU-ARG-PRO-GLY-NH2

Preferred Name

English

nafarelin [INN]

Common Name

English

NAFARELIN [VANDF]

Common Name

English

LHRH, 6(D-NAL(2))

Common Name

English

NAFARELIN [MI]

Common Name

English

Nafarelin [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1910