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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 of NAFARELIN

SMILES

CC(C)C[C@@]([H])(C(=N[C@@]([H])(CCCNC(=N)N)C(=O)N1CCC[C@@]1([H])C(=NCC(=N)O)O)O)N=C([C@@]([H])(Cc2ccc3ccccc3c2)N=C([C@]([H])(Cc4ccc(cc4)O)N=C([C@]([H])(CO)N=C([C@]([H])(Cc5c[nH]c6ccccc56)N=C([C@]([H])(Cc7cnc[nH]7)N=C([C@]8([H])CCC(=N8)O)O)O)O)O)O)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
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

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

6.3486722E11
Primary
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

6.3486722E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.02 ng/mL
304 μg single, nasal
dose: 304 μg
route of administration: Nasal
experiment type: SINGLE
co-administered: SODIUM GLYCOCHOLATE
NAFARELIN serum
Homo sapiens
population: UNKNOWN
age: ADULT
sex: MALE
food status: UNKNOWN
0.1 ng/mL
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
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
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
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
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7 ng × h/mL
304 μg single, nasal
dose: 304 μg
route of administration: Nasal
experiment type: SINGLE
co-administered: SODIUM GLYCOCHOLATE
NAFARELIN serum
Homo sapiens
population: UNKNOWN
age: ADULT
sex: MALE
food status: UNKNOWN
0.07 ng × h/mL
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
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.4 h
304 μg single, nasal
dose: 304 μg
route of administration: Nasal
experiment type: SINGLE
co-administered: SODIUM GLYCOCHOLATE
NAFARELIN serum
Homo sapiens
population: UNKNOWN
age: ADULT
sex: MALE
food status: UNKNOWN
2.7 h
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
Doses

Doses

DosePopulationAdverse 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:
healthy, adult
n = 18
Health Status: healthy
Age Group: adult
Sex: F
Population Size: 18
Sources:
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:
unhealthy, children
n = 155
Health Status: unhealthy
Condition: early puberty
Age Group: children
Sex: unknown
Population Size: 155
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Patents

Sample Use Guides

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
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
NAFARELIN [INN]
Common Name English
NAFARELIN [VANDF]
Common Name English
5-OXOPRO-HIS-TRP-SER-TYR-D-NAL(2)-LEU-ARG-PRO-GLY-NH2
Common Name English
NAFARELIN [WHO-DD]
Common Name English
LHRH, 6(D-NAL(2))
Common Name English
NAFARELIN [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1910
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
LIVERTOX 660
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
NDF-RT N0000009332
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
WHO-VATC QH01CA02
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
NDF-RT N0000175654
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
NDF-RT N0000175655
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
WHO-ATC H01CA02
Created by admin on Sat Jun 26 03:46:48 UTC 2021 , Edited by admin on Sat Jun 26 03:46:48 UTC 2021
Code System Code Type Description
WIKIPEDIA
Nafarelin
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
PRIMARY
MERCK INDEX
M7705
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
PRIMARY Merck Index
MESH
D017274
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
PRIMARY
DRUG CENTRAL
1868
Created by admin on Sat Jun 26 03:46:48 UTC 2021 , Edited by admin on Sat Jun 26 03:46:48 UTC 2021
PRIMARY
FDA UNII
1X0094V6JV
Created by admin on Sat Jun 26 03:46:48 UTC 2021 , Edited by admin on Sat Jun 26 03:46:48 UTC 2021
PRIMARY
EVMPD
SUB09115MIG
Created by admin on Sat Jun 26 03:46:48 UTC 2021 , Edited by admin on Sat Jun 26 03:46:48 UTC 2021
PRIMARY
ChEMBL
CHEMBL1201309
Created by admin on Sat Jun 26 03:46:48 UTC 2021 , Edited by admin on Sat Jun 26 03:46:48 UTC 2021
PRIMARY
DRUG BANK
DB00666
Created by admin on Sat Jun 26 03:46:48 UTC 2021 , Edited by admin on Sat Jun 26 03:46:48 UTC 2021
PRIMARY
NCI_THESAURUS
C61613
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
PRIMARY
IUPHAR
3902
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
PRIMARY
PUBCHEM
25077405
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
PRIMARY
RXCUI
28656
Created by admin on Sat Jun 26 03:46:49 UTC 2021 , Edited by admin on Sat Jun 26 03:46:49 UTC 2021
PRIMARY RxNorm
CAS
76932-56-4
Created by admin on Sat Jun 26 03:46:48 UTC 2021 , Edited by admin on Sat Jun 26 03:46:48 UTC 2021
PRIMARY
INN
5402
Created by admin on Sat Jun 26 03:46:48 UTC 2021 , Edited by admin on Sat Jun 26 03:46:48 UTC 2021
PRIMARY