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

[H][C@@]12CC[C@@](O)(CC#N)[C@@]1(C)CCC3=C4CCC(=O)C=C4CC[C@@]23[H]

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

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 2678	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 1064	950.0 nM [IC50]
Corticosteroid binding globulin 4 Target ID: CHEMBL2421 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18061638	Binding Agent 1064	7.97 µM [IC50]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18061638	Antagonist 2778	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 8429	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 8429	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 8429	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) n = 102 Health Status: healthy Age Group: 23 years (range: 18-35 years) Sex: F Population Size: 102 Sources: https://pubmed.ncbi.nlm.nih.gov/22128200	Sources: https://pubmed.ncbi.nlm.nih.gov/22128200

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 CYP2E1 882	CYP1A 22 CYP2A6 543 CYP2B6 664 CYP2E1 667 CYP1A2 1054 CYP2C19 991

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 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 1553	inhibitor 3277 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 1819	inhibitor 3277 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 1891	inhibitor 3277 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 970	inhibitor 3277 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 1925	inhibitor 3277 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 1737	substrate 3367 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 22	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25 Page: 25.0	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 121-122	no
CYP2A6 543	substrate 3367 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 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25 Page: 25.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 121-122	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_ClinPharmR.pdf#page=122 Page: (ClinPharm) 121-122	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022252_Orig-1_PharmR.pdf#page=25 Page: 25.0	no
CYP2E1 667	substrate 3367 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 1647	inhibitor 1626 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
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
eMolecules	29934821	https://www.emolecules.com/cgi-bin/more?vid=29934821
eMolecules	32456343	https://www.emolecules.com/cgi-bin/more?vid=32456343

PubMed

Title	Date	PubMed
Effect of four oral contraceptives on hemostatic parameters.	2004 Aug	15288212
Dienogest inhibits Toll-like receptor 4 expression induced by costimulation of lipopolysaccharide and high-mobility group box 1 in endometrial epithelial cells.	2011 Dec	22014880
Progestin effects on expression of AKR1C1-AKR1C3, SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line.	2013 Feb 25	23183084

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.

Name

Type

Language

DIENOGEST

Official 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-17α-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