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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H25NO2
Molecular Weight 311.4187
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIENOGEST

SMILES

C[C@@]12CCC3=C4CCC(=O)C=C4CC[C@@]3([H])[C@]2([H])CC[C@]1(CC#N)O

InChI

InChIKey=AZFLJNIPTRTECV-FUMNGEBKSA-N
InChI=1S/C20H25NO2/c1-19-8-6-16-15-5-3-14(22)12-13(15)2-4-17(16)18(19)7-9-20(19,23)10-11-21/h12,17-18,23H,2-10H2,1H3/t17-,18+,19+,20-/m1/s1

HIDE SMILES / InChI

Molecular Formula C20H25NO2
Molecular Weight 311.4187
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/9829156 | https://www.drugs.com/pro/natazia.html

Dienogest (Natazia) is a hybrid progestogen that combines properties of both the 19-nortestosterone derivatives and the progesterone derivatives. It is indicated for use by women to prevent pregnancy and for the treatment of heavy menstrual bleeding in women without organic pathology. Dienogest is also approved in Europe, Australia, Malaysia, Singapore and Japan for the treatment of endometriosis. It is lowers the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation. Dienogest exhibits highly selective binding to the progesterone receptor. It has high progestational and significant antiandrogenic activity, but only moderate antigonadotrophic activity. The most common adverse reactions in clinical trials for Natazia are headache (including migraines), breast pain, menstrual disorders, nausea or vomiting, acne, mood changes and increased weight.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.4 nM [EC50]
Target ID: P04278|||Q6ISD2
Gene ID: 6462.0
Gene Symbol: SHBG
Target Organism: Homo sapiens (Human)
950.0 nM [IC50]
7.97 µM [IC50]
420.0 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NATAZIA

Approved Use

Natazia® is indicated for use by women to prevent pregnancy. It is also indicated for the treatment of heavy menstrual bleeding in women without organic pathology who choose to use an oral contraceptive as their method of contraception.

Launch Date

1.27310404E12
Preventing
NATAZIA

Approved Use

Natazia® is indicated for use by women to prevent pregnancy. It is also indicated for the treatment of heavy menstrual bleeding in women without organic pathology who choose to use an oral contraceptive as their method of contraception.

Launch Date

1.27310404E12
Primary
NATAZIA

Approved Use

Dienogest is approved as a monotherapy for the treatment of endometriosis.

Launch Date

1.27310404E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
85.2 ng/mL
3 mg 1 times / day steady-state, oral
dose: 3 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: ESTRADIOL
DIENOGEST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
110.41 ng/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIENOGEST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
828 ng × h/mL
3 mg 1 times / day steady-state, oral
dose: 3 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: ESTRADIOL
DIENOGEST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
1827.014 ng × h/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIENOGEST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.3 h
3 mg 1 times / day steady-state, oral
dose: 3 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: ESTRADIOL
DIENOGEST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
14.82 h
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIENOGEST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
3 mg 1 times / day steady-state, oral
dose: 3 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: ESTRADIOL
DIENOGEST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
3 mg 1 times / day multiple, oral
Highest studied dose
Dose: 3 mg, 1 times / day
Route: oral
Route: multiple
Dose: 3 mg, 1 times / day
Sources:
healthy, 23 years (range: 18-35 years)
n = 102
Health Status: healthy
Age Group: 23 years (range: 18-35 years)
Sex: F
Population Size: 102
Sources:
Overview

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no (co-administration study)
Comment: Human liver microsomes; Co-administration of 0.03 mg EE/2 mg DNG (over 21 days) did not have any effect on 10 mg nifedipine (CYP3A4 substrate, Day 21) PK (decreased Cmax by 2.1% and AUC(0-inf) by 2.4%).
Page: (ClinPharm) 9, 27-28, 121-122, 136
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: Microsomes expressing CYP3A4; Co-administration of 600 mg rifampicin (strong CYP3A4 inducer) daily (Days 12-16) with 2 mg EV/3 mg DNG tablets (over 17 days) resulted in a 52 % decrease in the mean Cmax and a 83% in the AUC(0-24) for DNG. Co-administration of 400 mg ketoconazole (strong CYP3A4 inhibitor, Days 8-14) daily with 2 mg EV/3 mg DNG tablets (14 days) resulted in a 94% increase in the mean Cmax and a 186% increase in the AUC(0-24) for DNG. Co-administration of 1500 mg erythromycin (moderate CYP3A4 inhibitor, 500 mg TID on Days 8-14) daily with EV/DNG tablets (14 days) resulted in a 33% increase in the mean Cmax and a 62% increase in the AUC(0-24) for DNG.
Page: 25, (ClinPharm) 8-9, 22, 25, 26-27, 82-98, 100-108, 121-122
no
no
no
no
no
no
no
no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
The efficacy and tolerability of Valette: a postmarketing surveillance study.
1999 Sep
A comparative study of the effects of two oral contraceptives containing dienogest or desogestrel on the human immune system.
2000 Feb
Effects of two oral contraceptives on plasma levels of insulin-like growth factor I (IGF-I) and growth hormone (hGH).
2000 Nov
Non-protein bound dienogest in serum and salivary dienogest in women taking the oral contraceptives Certostat and Valette.
2001 Apr
Clinical findings with the oral contraceptive combination ethinylestradiol/dienogest in the Czech Republic.
2002 Dec
Twenty-one day administration of dienogest reversibly suppresses gonadotropins and testosterone in normal men.
2002 May
Effect of four oral contraceptives on hemostatic parameters.
2004 Aug
Effects of raloxifene, hormone therapy, and soy isoflavone on serum high-sensitive C-reactive protein in postmenopausal women.
2005 Aug
Progesterone and progestational compounds attenuate tumor necrosis factor alpha-induced interleukin-8 production via nuclear factor kappa B inactivation in endometriotic stromal cells.
2005 May
Dienogest inhibits Toll-like receptor 4 expression induced by costimulation of lipopolysaccharide and high-mobility group box 1 in endometrial epithelial cells.
2011 Dec
Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E₂ production in human endometriotic stromal cells in spheroid culture.
2012 Feb
Progestin effects on expression of AKR1C1-AKR1C3, SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line.
2013 Feb 25
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: estradiol valerate/dienogest
One tablet daily by mouth at the same time every day. Tablets must be taken in the order directed on the blister pack. Do not skip or delay intake by more than 12 hours.
Route of Administration: Oral
After 12 days in the presence of oestradiol (10(-8) mol/l) plus dienogest (10(-6) mol/l), cultured human endometrial stromal cells underwent morphological differentiation and produced prolactin, a typical marker for decidualization.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:07:57 UTC 2021
Edited
by admin
on Fri Jun 25 21:07:57 UTC 2021
Record UNII
46M3EV8HHE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DIENOGEST
DASH   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
DIENOGEST [WHO-DD]
Common Name English
ENDOMETRION
Brand Name English
DIENOGEST [INN]
Common Name English
M-18575
Code English
19-NORPREGNA-4,9-DIENE-21-NITRILE, 17-HYDROXY-3-OXO-, (17.ALPHA.)-
Common Name English
DIENOGEST [VANDF]
Common Name English
STS-557
Code English
STS 557
Code English
17-HYDROXY-3-OXO-19-NOR-17.ALPHA.-PREGNA-4,9-DIENE-21-NITRILE
Common Name English
ZK 37659
Code English
DIENOGEST [USAN]
Common Name English
DIENOGEST [MI]
Common Name English
DIENOGEST [ORANGE BOOK]
Common Name English
M 18575
Code English
DIENOGEST [MART.]
Common Name English
MJR-35
Code English
DIENOGEST [JAN]
Common Name English
ZK-37659
Code English
DIENOGEST [EP MONOGRAPH]
Common Name English
Classification Tree Code System Code
WHO-VATC QG03FA15
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
WHO-ATC G03FA15
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
NDF-RT N0000175602
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
WHO-VATC QG03AB08
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
WHO-VATC QG03DB08
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
WHO-ATC G03AB08
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
WHO-VATC QG03AA16
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
NCI_THESAURUS C776
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
WHO-ATC G03AA16
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
WHO-ATC G03DB08
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
LIVERTOX 302
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
Code System Code Type Description
WIKIPEDIA
DIENOGEST
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
EVMPD
SUB07108MIG
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
PUBCHEM
68861
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
LACTMED
Dienogest
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
MESH
C023635
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
IUPHAR
7654
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
INN
5286
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
RXCUI
22968
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C87238
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
DRUG BANK
DB08866
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
FDA UNII
46M3EV8HHE
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
MERCK INDEX
M4387
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
871
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
CAS
65928-58-7
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
ChEMBL
CHEMBL1201864
Created by admin on Fri Jun 25 21:07:57 UTC 2021 , Edited by admin on Fri Jun 25 21:07:57 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> AGONIST
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SINGLE DOSE

Tmax PHARMACOKINETIC SINGLE DOSE

Volume of Distribution PHARMACOKINETIC IV administration