GESTRINONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H24O2
Molecular Weight	308.4141
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC[C@]12C=CC3=C4CCC(=O)C=C4CC[C@H]3[C@@H]1CC[C@@]2(O)C#C

InChI

InChIKey=BJJXHLWLUDYTGC-ANULTFPQSA-N

InChI=1S/C21H24O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,9,11,13,18-19,23H,3,5-8,10,12H2,1H3/t18-,19+,20+,21+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://gp2u.com.au/static/pdf/D/DIMETRIOSE-PI.pdf

Gestrinone is a synthetic trienic 19-norsteroid developed for the treatment of endometriosis. Gestrinone exerts its activity by activating androgen and progesterone receptors. The drug was approved for use in Latin America, Australia and Europe.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen receptor 42 Target ID: P10275 Gene ID: 367.0 Gene Symbol: AR Target Organism: Homo sapiens (Human) Sources: https://gp2u.com.au/static/pdf/D/DIMETRIOSE-PI.pdf	Agonist 2752		0.59 nM [EC50]
Progesterone receptor 61 Target ID: P06401 Gene ID: 5241.0 Gene Symbol: PGR Target Organism: Homo sapiens (Human) Sources: https://gp2u.com.au/static/pdf/D/DIMETRIOSE-PI.pdf	Agonist 2752		30.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Endometriosis 32 Sources: https://gp2u.com.au/static/pdf/D/DIMETRIOSE-PI.pdf	Primary		Approved 8583	DIMETRIOSE Approved Use Mild to moderate endometriosis with or without accompanying sterility. Treatment is limited to a single course of six months duration per lifetime.

C_max

Value	Dose	Co-administered	Analyte	Population
19 ng/mL OTHER GOV'T https://gp2u.com.au/static/pdf/D/DIMETRIOSE-PI.pdf	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		GESTRINONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
5 mg 3 times / week multiple, oral Studied dose Dose: 5 mg, 3 times / week Route: oral Route: multiple Dose: 5 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/	unhealthy Health Status: unhealthy Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/	Other AEs: weight gai, Seborrhea... Other AEs: weight gai Seborrhea Acne Hirsutism (10%) Hoarseness (10%) Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/

AEs

AE	Significance	Dose	Population
Acne		5 mg 3 times / week multiple, oral Studied dose Dose: 5 mg, 3 times / week Route: oral Route: multiple Dose: 5 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/	unhealthy Health Status: unhealthy Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/
Seborrhea		5 mg 3 times / week multiple, oral Studied dose Dose: 5 mg, 3 times / week Route: oral Route: multiple Dose: 5 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/	unhealthy Health Status: unhealthy Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/
weight gai		5 mg 3 times / week multiple, oral Studied dose Dose: 5 mg, 3 times / week Route: oral Route: multiple Dose: 5 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/	unhealthy Health Status: unhealthy Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/
Hirsutism	10%	5 mg 3 times / week multiple, oral Studied dose Dose: 5 mg, 3 times / week Route: oral Route: multiple Dose: 5 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/	unhealthy Health Status: unhealthy Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/
Hoarseness	10%	5 mg 3 times / week multiple, oral Studied dose Dose: 5 mg, 3 times / week Route: oral Route: multiple Dose: 5 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/	unhealthy Health Status: unhealthy Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2694740/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057		CYP19A1 1

Drug as perpetrator

Target	Modality	Activity
CYP19A1 430	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/20112494/	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671199#sid=170466364	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144206014	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671198#sid=170466364	yes [IC50 0.7762 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170466364	yes [IC50 0.9772 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466364	yes [IC50 1.2302 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671197#sid=170466364	yes [IC50 2.4545 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=144206014

PubMed

Title	Date	PubMed
Vaginal adenosarcoma arising from refractory endometriosis: a case report.	2010-12	21133871
Enzyme-linked immunosorbent assays for the synthetic steroid gestrinone.	2010-09-15	20801376
Endometriosis.	2010-08-13	21418683
A rapid screening LC-MS/MS method based on conventional HPLC pumps for the analysis of low molecular weight xenobiotics: application to doping control analysis.	2010-07	20818799
Gestrinone compared with mifepristone for emergency contraception: a randomized controlled trial.	2010-04	20308833
Generic sample preparation combined with high-resolution liquid chromatography-time-of-flight mass spectrometry for unification of urine screening in doping-control laboratories.	2010-04	20155493
The progins progesterone receptor gene polymorphism is not related to endometriosis-associated infertility or to idiopathic infertility.	2010	21243274
[Treatment for endometriosis].	2009-12-10	19994769
Effect of Yikun Neiyi Wan on the expression of aromatase P450, COX-2, and ER related receptor in endometrial cells in vitro from patients with endometriosis.	2009-12	20112494
Tetrahydrogestrinone analysis and designer steroids revisited.	2009-11	21083096
Endometriosis in Italy: from cost estimates to new medical treatment.	2009-11	19908951
Endometriosis presenting as an acute groin swelling: a case report.	2009-08-12	19918584
Searching for in silico predicted metabolites and designer modifications of (cortico)steroids in urine by high-resolution liquid chromatography/time-of-flight mass spectrometry.	2009-08	19575408
Chinese herbal medicine for endometriosis.	2009-07-08	19588398
Ovulation-stimulation drugs and cancer risks: a long-term follow-up of a British cohort.	2009-06-02	19436296
A simple and rapid ESI-LC-MS/MS method for simultaneous screening of doping agents in urine samples.	2009-04	20336223
Detection and pharmacokinetics of tetrahydrogestrinone in horses.	2009-04	19290951
Endometriosis: current therapies and new pharmacological developments.	2009	19405548
Treatment of pelvic pain associated with endometriosis.	2008-11	19007642
Detection of anabolic steroid abuse using a yeast transactivation system.	2008-10	18550137
Does gestrinone antagonize the effects of estrogen on endometrial implants upon the peritoneum of rats?	2008-08	18719766
Medical management of fibroids.	2008-08	18468953
Recognising, understanding and managing endometriosis.	2008-07	19562047
[Determination of three anabolic steroids by liquid chromatography-mass spectrometry].	2008-07	18959243
Comprehensive screening of acidic and neutral drugs in equine plasma by liquid chromatography-tandem mass spectrometry.	2008-05-02	18054785
Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay.	2008-05	18395441
Endometriosis: current and future medical therapies.	2008-04	18036995
Induction of micronuclei in V79 cells by the anabolic doping steroids tetrahydrogestrinone and trenbolone.	2008-04	17764006
Screening of in vitro synthesised metabolites of 4,9,11-trien-3-one steroids by liquid chromatography mass spectrometry.	2008	18708698
Structural characterization of the human androgen receptor ligand-binding domain complexed with EM5744, a rationally designed steroidal ligand bearing a bulky chain directed toward helix 12.	2007-10-19	17711855
Mechanism of emergency contraception with gestrinone: a preliminary investigation.	2007-09	17707720
Nanomolar concentrations of anabolic-androgenic steroids amplify excitotoxic neuronal death in mixed mouse cortical cultures.	2007-08-24	17662261
Neuroendocrine-immune disequilibrium and endometriosis: an interdisciplinary approach.	2007-06	17621704
Expressions of VEGF and Ki-67 in eutopic endometrium of patients with endometriosis and effect of Quyu Jiedu Recipe on VEGF expression.	2007-06	17609908
Analysis of synthetic 19-norsteroids trenbolone, tetrahydrogestrinone and gestrinone by gas chromatography-mass spectrometry.	2007-05-25	16963059
Preparation of antibodies for the designer steroid tetrahydrogestrinone and development of an enzyme-linked immunosorbent assay for human urine analysis.	2007-05-15	17441677
Effects of gestrinone on uterine leiomyoma and expression of c-Src in a guinea pig model.	2007-05	17439725
Breast pain.	2007-04-01	19454068
Multi-detection of corticosteroids in sports doping and veterinary control using high-resolution liquid chromatography/time-of-flight mass spectrometry.	2007-03-14	17386705
Endometriosis.	2007-03-01	19454060
[Outcome analysis of stage III - IV endometriosis after conservative surgery].	2007-02	17442181
Preoperative treatment for hysteroscopic surgery.	2006-10	16926013
Comparative study on the efficacy of Yiweining and Gestrinone for post-operational treatment of stage III endometriosis.	2006-09	17005086
Games of hormones: the para-endocrinology of sport.	2006-08-12	16901804
Doping control analysis in human urine by liquid chromatography-electrospray ionization ion trap mass spectrometry for the Olympic Games Athens 2004: determination of corticosteroids and quantification of ephedrines, salbutamol and morphine.	2006-07-28	17723530
Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG).	2006-07	16797178
The role of progestins in treating the pain of endometriosis.	2006-06-06	17097575
Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity.	2006-05	16641486
[Anti progestins].	2006-04	16689349
A fast liquid chromatographic/mass spectrometric screening method for the simultaneous detection of synthetic glucocorticoids, some stimulants, anti-oestrogen drugs and synthetic anabolic steroids.	2006	17066372

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage is one capsule twice a week. The first dose should be taken on the first day of a menstrual cycle. The second dose should be taken three days later.

Route of Administration: Oral

In Vitro Use Guide

Ectopic endometrium cells were cultured and exposed to gestrinone of different doses of 0, 10(-6) and 10(-4) mol/L respectively. The inhibition of the cells during 48 hours was determined by methylthiazolyl tetrazolium (MTT) assay, and the cell growth curve was made. Gestrinone at different concentrations could inhibit the growth and proliferation of ectopic endometrium cells in a dose- and time-dependent manner. The inhibition rate of cell growth after exposed to gestrinone for 8, 16, 24, 32, 40 and 48 h was 99.6%, 87.3%, 79.8%, 62.3%, 51.7% and 44.2% in the 10(-6) mol/L group, and 99.2%, 77.1%, 69.6%, 51.1%, 33.7% and 23.6% in the 10(-4) mol/L group (P < 0.05), and cell growth curve was changed accordingly. After 24 hour exposure to gestrinone from 10(-6) to 10(-4) mol/l, apoptotic changes of cells were observed under transmission electron microscope.

Name

Type

Language

A 46 745

Preferred Name

English

GESTRINONE

Official Name

English

RU 2323

Code

English

GESTRINONE [MI]

Common Name

English

13-Ethyl-17-hydroxy-18,19-dinor-17?-pregna-4,9,11-trien-20-yn-3-one

Systematic Name

English

RU-2323

Code

English

GESTRINONE [MART.]

Common Name

English

R-2323

Code

English

gestrinone [INN]

Common Name

English

Gestrinone [WHO-DD]

Common Name

English

PREGNA-4,9,11-TRIEN-20-YN-3-ONE, 13-ETHYL-17-HYDROXY-18,19-DINOR-, (17.ALPHA.)-

Common Name

English

A-46745

Code

English

R 2323

Code

English

18,19-DINORPREGNA-4,9,11-TRIEN-20-YN-3-ONE, 13-ETHYL-17-HYDROXY-, (17.ALPHA.)-

Systematic Name

English

GESTRINONE [USAN]

Common Name

English

A-46-745

Code

English

GESTRINONE [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C776