U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C66H86N18O12
Molecular Weight 1323.505
Optical Activity UNSPECIFIED
Defined Stereocenters 9 / 9
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of HISTRELIN

SMILES

CCN=C([C@]1([H])CCCN1C(=O)[C@]([H])(CCCNC(=N)N)N=C([C@]([H])(CC(C)C)N=C([C@@]([H])(Cc2cn(Cc3ccccc3)cn2)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)O)O

InChI

InChIKey=HHXHVIJIIXKSOE-QILQGKCVSA-N
InChI=1S/C66H86N18O12/c1-4-70-64(95)55-17-11-25-84(55)65(96)48(16-10-24-71-66(67)68)76-58(89)49(26-38(2)3)77-62(93)53(30-43-34-83(37-74-43)33-40-12-6-5-7-13-40)81-59(90)50(27-39-18-20-44(86)21-19-39)78-63(94)54(35-85)82-60(91)51(28-41-31-72-46-15-9-8-14-45(41)46)79-61(92)52(29-42-32-69-36-73-42)80-57(88)47-22-23-56(87)75-47/h5-9,12-15,18-21,31-32,34,36-38,47-55,72,85-86H,4,10-11,16-17,22-30,33,35H2,1-3H3,(H,69,73)(H,70,95)(H,75,87)(H,76,89)(H,77,93)(H,78,94)(H,79,92)(H,80,88)(H,81,90)(H,82,91)(H4,67,68,71)/t47-,48-,49-,50-,51-,52-,53+,54-,55-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/vantas.html

Histrelin is a gonadotropin releasing hormone (GnRH) agonist that acts as a potent inhibitor of gonadotropin when administered as an implant that delivers continuous therapeutic doses. Following an initial stimulatory phase with increased circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to a transient increase in concentration of gonadal steroids (testosterone and dihydrotestosterone in males), continuous administration of histrelin acetate results in decreased levels of LH and FSH due to a reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes. As the product Supprelin LA (FDA), histrelin is indicated for the treatment of children with central precocious puberty (CPP). As the product Vantas (FDA), histrelin is indicated for the palliative treatment of advanced prostate cancer.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Vantas

Approved Use

Vantas is indicated for the palliative treatment of advanced prostate cancer.

Launch Date

1.09745281E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.1 ng/mL
50 μg 1 times / day steady-state, subcutaneous implant
dose: 50 μg
route of administration: Subcutaneous implant
experiment type: STEADY-STATE
co-administered:
HISTRELIN serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
0.398 ng × week/mL
50 μg 1 times / day steady-state, subcutaneous implant
dose: 50 μg
route of administration: Subcutaneous implant
experiment type: STEADY-STATE
co-administered:
HISTRELIN serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4 h
50 μg 1 times / day steady-state, subcutaneous implant
dose: 50 μg
route of administration: Subcutaneous implant
experiment type: STEADY-STATE
co-administered:
HISTRELIN serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.92 h
500 μg single, subcutaneous
dose: 500 μg
route of administration: Subcutaneous
experiment type: SINGLE
co-administered:
HISTRELIN unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
29.5%
500 μg single, subcutaneous
dose: 500 μg
route of administration: Subcutaneous
experiment type: SINGLE
co-administered:
HISTRELIN unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
65 ug 1 times / day steady, subdermal
Recommended
Dose: 65 ug, 1 times / day
Route: subdermal
Route: steady
Dose: 65 ug, 1 times / day
Sources: Page: 14
unhealthy, children
n = 47
Health Status: unhealthy
Condition: central precocious puberty
Age Group: children
Sex: M+F
Population Size: 47
Sources: Page: 14
Disc. AE: Implant site infection...
AEs leading to
discontinuation/dose reduction:
Implant site infection (1 patient)
Sources: Page: 14
AEs

AEs

AESignificanceDosePopulation
Implant site infection 1 patient
Disc. AE
65 ug 1 times / day steady, subdermal
Recommended
Dose: 65 ug, 1 times / day
Route: subdermal
Route: steady
Dose: 65 ug, 1 times / day
Sources: Page: 14
unhealthy, children
n = 47
Health Status: unhealthy
Condition: central precocious puberty
Age Group: children
Sex: M+F
Population Size: 47
Sources: Page: 14
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Histrelin for central precocious puberty-a single surgeon experience.
2015 Oct
Experience with the Histrelin Implant in Pediatric Patients.
2016
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: The implant is inserted subcutaneously in the inner aspect of the upper arm
The recommended dose of VANTAS is one implant for 12 months. Each implant contains 50 mg histrelin acetate to deliver 41 mg histrelin. The implant is inserted subcutaneously in the inner aspect of the upper arm and provides continuous release of histrelin (50 mcg/day) for 12 months of hormonal therapy. VANTAS should be removed after 12 months of therapy
Route of Administration: Other
Histrelin at concentrations of 10(-7)M and 10(-8) M (a concentration of 10(-7) M was more effective than 10(-8) M), stimulated significantly VP secretion from isolated rat hypothalamo-neurohypophysial explants
Name Type Language
HISTRELIN
HSDB   INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
HISTRELIN [WHO-DD]
Common Name English
LUTEINIZING HORMONE-RELEASING FACTOR (PIG), 6-(1-(PHENYLMETHYL)-D-HISTIDINE)-9-(N-ETHYL-L-PROLINAMIDE)-10-DEGLYCINAMIDE-
Common Name English
HISTRELIN [INN]
Common Name English
HISTRELIN [USAN]
Common Name English
5-OXO-L-PROLYL-L-HISTIDYL-L-TRYPTOPHYL-L-SERYL-L-TYROSYL-NT-BENZYL-D-HISTIDYL-L-LEUCYL-L-ARGINYL-N-ETHYL-L-PROLINAMIDE
Common Name English
HISTRELIN [MI]
Common Name English
HISTRELIN [HSDB]
Common Name English
ORF-17070
Code English
HISTRELIN [VANDF]
Common Name English
ORF 17070RWJ 17070
Code English
RWJ-17070
Code English
HISTRELIN [MART.]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175654
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
WHO-VATC QL02AE05
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
FDA ORPHAN DRUG 212605
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
NCI_THESAURUS C1910
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
FDA ORPHAN DRUG 28488
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
WHO-ATC L02AE05
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
NDF-RT N0000175655
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
WHO-ATC H01CA03
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
Code System Code Type Description
DRUG BANK
DB06788
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
DRUG CENTRAL
2975
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
ChEMBL
CHEMBL1201255
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
EPA CompTox
76712-82-8
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
CAS
76712-82-8
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
IUPHAR
3884
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
MESH
C029256
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
HSDB
7657
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
EVMPD
SUB08046MIG
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
MERCK INDEX
M6030
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY Merck Index
PUBCHEM
25077993
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
RXCUI
50975
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY RxNorm
FDA UNII
H50H3S3W74
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
NCI_THESAURUS
C74270
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
WIKIPEDIA
HISTRELIN
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY
INN
5733
Created by admin on Sat Jun 26 11:59:25 UTC 2021 , Edited by admin on Sat Jun 26 11:59:25 UTC 2021
PRIMARY