Histrelin

Names

[ Name ]:
Histrelin

[Synonym ]:
histreline
6-(1-(Phenylmethyl)-D-histidine)-9-(N-ethyl-L-prolinamide)-10-deglycinamideluteinizing hormone-releasing fFactor
histrelinum
HISTRELIN
5-Oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-1-benzyl-D-histidyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide
L-Prolinamide, 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-1-(phenylmethyl)-D-histidyl-L-leucyl-L-arginyl-N-ethyl-
MFCD00133494
histrelina
(Des-Gly10,His(Bzl)6,Pro-NHEt9)-LHRH

Biological Activity

[Description]:

Histrelin, a GnRH analogue, is a GnRH Receptor agonist. Histrelin increases serum luteinising hormone (LH), follicle stimulating hormone (FSH) and testosterone levels. Histrelin can be used in the research of prostate cancer, endometriosis[1][2][5].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> GNRH Receptor

Research Areas >> Cancer

[Target]

GnRH Receptor[1]

[In Vitro]

Histrelin (10-100 nM) stimulates the release of vasopressin (VP) from from isolated rat hypothalamo-neurohypophysial explants[4]. Histrelin (100 nM) stimulates oxytocin (OT) release from the rat hypothalamo-neurohypophysial system[5].

[In Vivo]

Histrelin (0.1 mg/kg, subcutaneous injection) rescues the circulating LH concentrations in Csfmop/Csfmop mice[2]. Histrelin (10,30, or 100 μg /day, subcutaneous injection) reduces the number of endometrial glands and atrophied the stroma in rabbits[3]. Animal Model: Csfmop/Csfmop mice [2] Dosage: 0.001, 0.05, and 0.1 mg/kg Administration: Subcutaneous injection Result: Increased serum FSH concentrations by 4-fold. Animal Model: Rabbits[3] Dosage: 10, 30, or 100 μg /day Administration: Subcutaneous injection for 4 weeks Result: Caused a regression of the endometrial glands and a thinning of the stroma.

[References]

[1]. Emma D Deeks, et al. Histrelin: in advanced prostate cancer. Drugs. 2010 Mar 26;70(5):623-30.

[2]. P E Cohen, et al. Colony-stimulating factor-1 plays a major role in the development of reproductive function in male mice. Mol Endocrinol. 1997 Oct;11(11):1636-50.

[3]. D W Hahn, et al. Development of an animal model for quantitatively evaluating effects of drugs on endometriosis. Fertil Steril. 1985 Sep;44(3):410-5.

[4]. E Boczek-Leszczyk, et al. Vasopressin release from the rat hypothalamo-neurohypophysial system: effects of gonadotrophin-releasing hormone (GnRH), its analogues and melatonin. J Physiol Pharmacol. 2010 Aug;61(4):459-66.

[5]. Marlena Juszczak, et al. Hypothalamic gonadotropin-releasing hormone receptor activation stimulates oxytocin release from the rat hypothalamo-neurohypophysial system while melatonin inhibits this process. Brain Res Bull. 2010 Jan 15;81(1):185-90.

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
1800.6ºC at 760 mmHg

[ Molecular Formula ]:
C₆₆H₈₆N₁₈O₁₂

[ Molecular Weight ]:
1323.502

[ Flash Point ]:
1042.8ºC

[ Exact Mass ]:
1322.667236

[ PSA ]:
446.86000

[ LogP ]:
0.09

[ Index of Refraction ]:
1.701

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: OK6370800

CHEMICAL NAME :: Luteinizing hormone releasing factor (pig), 6-(1-(phenylmethyl)-D-histidine)-9-(N-ethyl-L- prolinamide)-10-deglycinamide-

CAS REGISTRY NUMBER :: 76712-82-8

LAST UPDATED :: 199612

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C66-H86-N18-O12

MOLECULAR WEIGHT :: 1323.70

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 46 ug/kg

SEX/DURATION :: male 2 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Paternal Effects - other effects on male

REFERENCE :: JOAND3 Journal of Andrology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1980- Volume(issue)/page/year: 7,140,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 4667 ug/kg

SEX/DURATION :: male 8 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :: JOAND3 Journal of Andrology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1980- Volume(issue)/page/year: 7,140,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 2333 ug/kg

SEX/DURATION :: male 4 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

REFERENCE :: JOAND3 Journal of Andrology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1980- Volume(issue)/page/year: 7,140,1986

Safety Information

[ Symbol ]:

GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H360

[ Precautionary Statements ]:
P201-P308 + P313

[ Personal Protective Equipment ]:
Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
T: Toxic;

[ Risk Phrases ]:
R60

[ Safety Phrases ]:
53-22-36/37/39-45

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
OK6370800

[ HS Code ]:
2937190090

Customs

[ HS Code ]: 2937190090

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