HISTRELIN ACETATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C66H86N18O12.2C2H4O2
Molecular Weight	1443.6064
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)=O.CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2=CN(CC3=CC=CC=C3)C=N2)NC(=O)[C@H](CC4=CC=C(O)C=C4)NC(=O)[C@H](CO)NC(=O)[C@H](CC5=CNC6=C5C=CC=C6)NC(=O)[C@H](CC7=CNC=N7)NC(=O)[C@@H]8CCC(=O)N8

InChI

InChIKey=BKEMVGVBBDMHKL-VYFXDUNUSA-N

InChI=1S/C66H86N18O12.2C2H4O2/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;2*1-2(3)4/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);2*1H3,(H,3,4)/t47-,48-,49-,50-,51-,52-,53+,54-,55-;;/m0../s1

HIDE SMILES / InChI

Molecular Formula	C66H86N18O12
Molecular Weight	1323.5024
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	9 / 9
E/Z Centers	3
Optical Activity	UNSPECIFIED

Molecular Formula	C2H4O2
Molecular Weight	60.052
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB06788
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gonadotropin-releasing hormone receptor 41 Target ID: CHEMBL1855 Sources: http://www.drugbank.ca/drugs/DB06788	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced prostate cancer 9 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021732s000_Vantas_PrntLBLpdf.pdf	Palliative		Approved 8429	Vantas Approved Use Vantas is indicated for the palliative treatment of advanced prostate cancer. Launch Date 2004

C_max

Value	Dose	Co-administered	Analyte	Population
1.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16239357/	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

Value	Dose	Co-administered	Analyte	Population
0.398 ng × week/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16239357/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16239357/	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021732s022lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
29.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021732s022lbl.pdf	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

Dose	Population	Adverse 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022058s006lbl.pdf Page: 14	unhealthy, children n = 47 Health Status: unhealthy Condition: central precocious puberty Age Group: children Sex: M+F Population Size: 47 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022058s006lbl.pdf Page: 14	Disc. AE: Implant site infection... AEs leading to discontinuation/dose reduction: Implant site infection (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022058s006lbl.pdf Page: 14

AEs

AE	Significance	Dose	Population
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022058s006lbl.pdf Page: 14	unhealthy, children n = 47 Health Status: unhealthy Condition: central precocious puberty Age Group: children Sex: M+F Population Size: 47 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022058s006lbl.pdf Page: 14

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022058s000_PharmR.pdf#page=12 Page: 12.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5739	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5739
ChemicalBook	CB82493747	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB82493747

PubMed

Title	Date	PubMed
Histrelin for central precocious puberty-a single surgeon experience.	2015 Oct	25899147
Experience with the Histrelin Implant in Pediatric Patients.	2016	26683629

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:37:48 GMT 2023` Edited by `admin` on `Fri Dec 15 15:37:48 GMT 2023`
Record UNII	QMG7HLD1ZE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

HISTRELIN ACETATE

Common Name

English

SUPPRELIN

Brand Name

English

VANTAS

Brand Name

English

HISTRELIN ACETATE [ORANGE BOOK]

Common Name

English

HISTRELIN ACETATE [MART.]

Common Name

English

SUPPRELIN LA

Brand Name

English

Histrelin acetate [WHO-DD]

Common Name

English

HISTRELIN ACETATE [MI]

Common Name

English

HISTRELIN ACETATE [VANDF]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

16986