DIENOGEST

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H25NO2
Molecular Weight	311.418
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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	311.418
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022252s002lbl.pdf
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Progesterone receptor 61 Target ID: CHEMBL208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18061638	Agonist 2752	3.4 nM [EC50]
Sex hormone-binding globulin 1 Target ID: P04278\|\|\|Q6ISD2 Gene ID: 6462.0 Gene Symbol: SHBG Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/18061638	Binding Agent 1076	950.0 nM [IC50]
Corticosteroid binding globulin 4 Target ID: CHEMBL2421 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18061638	Binding Agent 1076	7.97 µM [IC50]
Androgen Receptor 169 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18061638	Antagonist 2849	420.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Heavy menstrual bleeding 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022252s002lbl.pdf	Primary	Approved 8583	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 2010
Pregnancy 65 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022252s002lbl.pdf	Preventing	Approved 8583	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 2010
Endometriosis 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27225336 https://www.ncbi.nlm.nih.gov/pubmed/20089522	Primary	Approved 8583	NATAZIA Approved Use Dienogest is approved as a monotherapy for the treatment of endometriosis. Launch Date 2010

C_max

Value	Dose	Co-administered	Analyte	Population
85.2 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022252s001lbl.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTRADIOL	ESTRADIOL	DIENOGEST plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
110.41 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24890474	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

Value	Dose	Co-administered	Analyte	Population
828 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022252s001lbl.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTRADIOL	ESTRADIOL	DIENOGEST plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1827.014 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24890474	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022252s001lbl.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTRADIOL	ESTRADIOL	DIENOGEST plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
14.82 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24890474	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022252s001lbl.pdf	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTRADIOL	ESTRADIOL	DIENOGEST plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/22128200	healthy, 23 years (range: 18-35 years) Health Status: healthy Age Group: 23 years (range: 18-35 years) Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/22128200	Sources: https://pubmed.ncbi.nlm.nih.gov/22128200

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057 CYP2E1 1060	CYP1A 26 CYP2A6 626 CYP2B6 776 CYP2E1 729 CYP1A2 1197 CYP2C19 1119

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 9, 27, 121-122	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 9, 27, 121-122	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 9, 27, 121-122	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 9, 27, 121-122	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 9, 27, 121-122	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=28, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=136 Page: (ClinPharm) 9, 27-28, 121-122, 136	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%). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=9, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=28, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=136 Page: (ClinPharm) 9, 27-28, 121-122, 136

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=8, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=25, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=27, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=97, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=107 Page: 25, (ClinPharm) 8-9, 22, 25, 26-27, 82-98, 100-108, 121-122	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=8, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=25, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=27, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=97, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=107 Page: 25, (ClinPharm) 8-9, 22, 25, 26-27, 82-98, 100-108, 121-122
CYP1A 26	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25 Page: 25.0	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 121-122	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=121 Page: 25, (ClinPharm) 121-122	no
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25 Page: 25.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 121-122	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 121-122	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25 Page: 25.0	no
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=121 Page: 25, (ClinPharm) 121-122	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=23 Page: 23.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:70708	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:70708
ChemicalBook	CB4947237	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4947237
eMolecules	29934821	https://www.emolecules.com/cgi-bin/more?vid=29934821
eMolecules	32456343	https://www.emolecules.com/cgi-bin/more?vid=32456343
MolPort	MolPort-006-393-664	https://www.molport.com/shop/molecule-link/MolPort-006-393-664
Selleck Chemicals	Dienogest	http://www.selleckchem.com/products/Dienogest.html
ZINC	ZINC000004215629	http://zinc15.docking.org/substances/ZINC000004215629

PubMed

Title	Date	PubMed
Progestin effects on expression of AKR1C1-AKR1C3, SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line.	2013-02-25	23183084
Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E₂ production in human endometriotic stromal cells in spheroid culture.	2012-02	22130322
Dienogest inhibits Toll-like receptor 4 expression induced by costimulation of lipopolysaccharide and high-mobility group box 1 in endometrial epithelial cells.	2011-12	22014880
Effects of raloxifene, hormone therapy, and soy isoflavone on serum high-sensitive C-reactive protein in postmenopausal women.	2005-08	15970291
Progesterone and progestational compounds attenuate tumor necrosis factor alpha-induced interleukin-8 production via nuclear factor kappa B inactivation in endometriotic stromal cells.	2005-05	15866594
Effect of four oral contraceptives on hemostatic parameters.	2004-08	15288212
Clinical findings with the oral contraceptive combination ethinylestradiol/dienogest in the Czech Republic.	2002-12	12616963
Twenty-one day administration of dienogest reversibly suppresses gonadotropins and testosterone in normal men.	2002-05	11994349
Non-protein bound dienogest in serum and salivary dienogest in women taking the oral contraceptives Certostat and Valette.	2001-04	11338674
Effects of two oral contraceptives on plasma levels of insulin-like growth factor I (IGF-I) and growth hormone (hGH).	2000-11	11172797
A comparative study of the effects of two oral contraceptives containing dienogest or desogestrel on the human immune system.	2000-02	10813102
The efficacy and tolerability of Valette: a postmarketing surveillance study.	1999-09	10574641

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Wed Apr 02 07:03:26 GMT 2025` Edited by `admin` on `Wed Apr 02 07:03:26 GMT 2025`
Record UNII	46M3EV8HHE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ENDOMETRION

Preferred Name

English

DIENOGEST

Official 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?-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

Dienogest [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QG03FA15