Identification

Name
Dydrogesterone
Accession Number
DB00378  (APRD00941)
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

A synthetic progestational hormone with no androgenic or estrogenic properties. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit ovulation. [PubChem]

Structure
Thumb
Synonyms
  • (9β,10α)-pregna-4,6-diene-3,20-dione
  • 10alpha-Isopregnenone
  • 6-Dehydro-retro-progesterone
  • 9β,10α-pregna-4,6-diene-3,20-dione
  • delta(6)-Retroprogesterone
  • delta(Sup 6)-retroprogesterone
  • Didrogesterona
  • Didrogesterone
  • Dydrogesterona
  • Dydrogestérone
  • Dydrogesterone
  • Dydrogesteronum
  • Gestatron
  • Hydrogesterone
  • Hydrogestrone
  • Isopregnenone
  • Retro-6-dehydroprogesterone
External IDs
NSC-92336
International/Other Brands
Dabroston (Abbott) / Dufaston (Abbott) / Duphaston (Abbott) / Terolut (Solvay)
Categories
UNII
90I02KLE8K
CAS number
152-62-5
Weight
Average: 312.4458
Monoisotopic: 312.20893014
Chemical Formula
C21H28O2
InChI Key
JGMOKGBVKVMRFX-HQZYFCCVSA-N
InChI
InChI=1S/C21H28O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h4-5,12,16-19H,6-11H2,1-3H3/t16-,17+,18-,19+,20+,21+/m0/s1
IUPAC Name
(1R,2S,10S,11S,14S,15S)-14-acetyl-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-6,8-dien-5-one
SMILES

Pharmacology

Indication

Used to treat irregular duration of cycles and irregular occurrence and duration of periods caused by progesterone deficiency. Also used to prevent natural abortion in patients who have a history of habitual abortions.

Structured Indications
Not Available
Pharmacodynamics

Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis.

Mechanism of action

Dydrogesterone is a progestogen that works by regulating the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus.

TargetActionsOrganism
AProgesterone receptor
agonist
Human
Absorption

Rapidly absorbed in the gastrointestinal tract with a bioavailability of 28%.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolism is complete to a 20-dihydrodydrogesterone (DHD) metabolite.

Route of elimination
Not Available
Half life

Dydrogesterone: 5-7 hours, 20-dihydrodydrogesterone (DHD) metabolite: 14-17 hours

Clearance
Not Available
Toxicity

No serious or unexpected toxicity has been observed with dydrogesterone. In acute toxicity studies, the LD50 doses in rats exceeded 4,640mg/kg for the oral route.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Dydrogesterone.Approved
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be decreased when used in combination with Dydrogesterone.Approved
AncrodThe therapeutic efficacy of Ancrod can be decreased when used in combination with Dydrogesterone.Investigational
Antithrombin III humanThe therapeutic efficacy of Antithrombin III human can be decreased when used in combination with Dydrogesterone.Approved
ApixabanThe therapeutic efficacy of Apixaban can be decreased when used in combination with Dydrogesterone.Approved
ArdeparinThe therapeutic efficacy of Ardeparin can be decreased when used in combination with Dydrogesterone.Approved, Investigational, Withdrawn
ArgatrobanThe therapeutic efficacy of Argatroban can be decreased when used in combination with Dydrogesterone.Approved, Investigational
BecaplerminThe therapeutic efficacy of Becaplermin can be decreased when used in combination with Dydrogesterone.Approved, Investigational
BivalirudinThe therapeutic efficacy of Bivalirudin can be decreased when used in combination with Dydrogesterone.Approved, Investigational
CertoparinThe therapeutic efficacy of Certoparin can be decreased when used in combination with Dydrogesterone.Approved, Investigational
Citric AcidThe therapeutic efficacy of Citric Acid can be decreased when used in combination with Dydrogesterone.Approved, Nutraceutical, Vet Approved
Conestat alfaDydrogesterone may increase the thrombogenic activities of Conestat alfa.Approved
Dabigatran etexilateThe therapeutic efficacy of Dabigatran etexilate can be decreased when used in combination with Dydrogesterone.Approved
DalteparinThe therapeutic efficacy of Dalteparin can be decreased when used in combination with Dydrogesterone.Approved
DanaparoidThe therapeutic efficacy of Danaparoid can be decreased when used in combination with Dydrogesterone.Approved, Withdrawn
DarexabanThe therapeutic efficacy of Darexaban can be decreased when used in combination with Dydrogesterone.Investigational
DesirudinThe therapeutic efficacy of Desirudin can be decreased when used in combination with Dydrogesterone.Approved
DextranThe therapeutic efficacy of Dextran can be decreased when used in combination with Dydrogesterone.Approved, Vet Approved
Dextran 40The therapeutic efficacy of Dextran 40 can be decreased when used in combination with Dydrogesterone.Approved
Dextran 70The therapeutic efficacy of Dextran 70 can be decreased when used in combination with Dydrogesterone.Approved
Dextran 75The therapeutic efficacy of Dextran 75 can be decreased when used in combination with Dydrogesterone.Approved
DicoumarolThe therapeutic efficacy of Dicoumarol can be decreased when used in combination with Dydrogesterone.Approved
Edetic AcidThe therapeutic efficacy of Edetic Acid can be decreased when used in combination with Dydrogesterone.Approved, Vet Approved
EdoxabanThe therapeutic efficacy of Edoxaban can be decreased when used in combination with Dydrogesterone.Approved
EnoxaparinThe therapeutic efficacy of Enoxaparin can be decreased when used in combination with Dydrogesterone.Approved
Ethyl biscoumacetateThe therapeutic efficacy of Ethyl biscoumacetate can be decreased when used in combination with Dydrogesterone.Withdrawn
Ferulic acidThe therapeutic efficacy of Ferulic acid can be decreased when used in combination with Dydrogesterone.Experimental
FluindioneThe therapeutic efficacy of Fluindione can be decreased when used in combination with Dydrogesterone.Investigational
FondaparinuxThe therapeutic efficacy of Fondaparinux can be decreased when used in combination with Dydrogesterone.Investigational
Fondaparinux sodiumThe therapeutic efficacy of Fondaparinux sodium can be decreased when used in combination with Dydrogesterone.Approved, Investigational
GabexateThe therapeutic efficacy of Gabexate can be decreased when used in combination with Dydrogesterone.Investigational
HeparinThe therapeutic efficacy of Heparin can be decreased when used in combination with Dydrogesterone.Approved, Investigational
Human C1-esterase inhibitorDydrogesterone may increase the thrombogenic activities of Human C1-esterase inhibitor.Approved
IdraparinuxThe therapeutic efficacy of Idraparinux can be decreased when used in combination with Dydrogesterone.Investigational
LepirudinThe therapeutic efficacy of Lepirudin can be decreased when used in combination with Dydrogesterone.Approved
LetaxabanThe therapeutic efficacy of Letaxaban can be decreased when used in combination with Dydrogesterone.Investigational
MelagatranThe therapeutic efficacy of Melagatran can be decreased when used in combination with Dydrogesterone.Experimental
NadroparinThe therapeutic efficacy of Nadroparin can be decreased when used in combination with Dydrogesterone.Approved
NafamostatThe therapeutic efficacy of Nafamostat can be decreased when used in combination with Dydrogesterone.Approved, Investigational
OtamixabanThe therapeutic efficacy of Otamixaban can be decreased when used in combination with Dydrogesterone.Investigational
Pentaerythritol TetranitrateThe therapeutic efficacy of Pentaerythritol Tetranitrate can be decreased when used in combination with Dydrogesterone.Approved
Pentosan PolysulfateThe therapeutic efficacy of Pentosan Polysulfate can be decreased when used in combination with Dydrogesterone.Approved
PhenindioneThe therapeutic efficacy of Phenindione can be decreased when used in combination with Dydrogesterone.Approved, Investigational
PhenprocoumonThe therapeutic efficacy of Phenprocoumon can be decreased when used in combination with Dydrogesterone.Approved, Investigational
Protein CThe therapeutic efficacy of Protein C can be decreased when used in combination with Dydrogesterone.Approved
Protein S humanThe therapeutic efficacy of Protein S human can be decreased when used in combination with Dydrogesterone.Approved
ProtocatechualdehydeThe therapeutic efficacy of Protocatechualdehyde can be decreased when used in combination with Dydrogesterone.Approved
ReviparinThe therapeutic efficacy of Reviparin can be decreased when used in combination with Dydrogesterone.Approved, Investigational
RivaroxabanThe therapeutic efficacy of Rivaroxaban can be decreased when used in combination with Dydrogesterone.Approved
SulodexideThe therapeutic efficacy of Sulodexide can be decreased when used in combination with Dydrogesterone.Approved, Investigational
TroxerutinThe therapeutic efficacy of Troxerutin can be decreased when used in combination with Dydrogesterone.Investigational
UlipristalThe therapeutic efficacy of Dydrogesterone can be decreased when used in combination with Ulipristal.Approved
WarfarinThe therapeutic efficacy of Warfarin can be decreased when used in combination with Dydrogesterone.Approved
XimelagatranThe therapeutic efficacy of Ximelagatran can be decreased when used in combination with Dydrogesterone.Approved, Investigational, Withdrawn
Food Interactions
Not Available

References

Synthesis Reference

Reerink, E.H., Westerhof, P. and Scholer, H.F.L.; U.S. Patent 3,198,792; assigned to North American Philips Company, Inc.

General References
  1. Link [Link]
External Links
Human Metabolome Database
HMDB14522
KEGG Drug
D01217
PubChem Compound
9051
PubChem Substance
46506195
ChemSpider
8699
ChEBI
31527
ChEMBL
CHEMBL1200853
Therapeutic Targets Database
DAP001205
PharmGKB
PA164745443
IUPHAR
2878
Guide to Pharmacology
GtP Drug Page
Wikipedia
Dydrogesterone
ATC Codes
G03FA14 — Dydrogesterone and estrogenG03DB01 — DydrogesteroneG03FB08 — Dydrogesterone and estrogen

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3CompletedPreventionPostmenopausal Syndrome1
2, 3Not Yet RecruitingTreatmentRecurrent Miscarriages1
3CompletedPreventionPreterm Delivery1
3CompletedTreatmentInfertility, Female2
3CompletedTreatmentRecurrent Miscarriages1
3CompletedTreatmentOne to five years postmenopausal2
3RecruitingTreatmentPregnancy1
4Not Yet RecruitingPreventionAbortion in First Trimester1
4RecruitingTreatmentRecurrent Pregnancy Losses1
Not AvailableActive Not RecruitingNot AvailableEndometriosis1
Not AvailableCompletedPreventionPremature Labour1
Not AvailableCompletedTreatmentLuteal Phase Defect1
Not AvailableCompletedTreatmentMenopausal and Postmenopausal Disorders1
Not AvailableRecruitingNot AvailableThreatened Miscarriage1
Not AvailableRecruitingPreventionIntrauterine Adhesions4

Pharmacoeconomics

Manufacturers
  • Solvay pharmaceuticals
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)168-169Reerink, E.H., Westerhof, P. and Scholer, H.F.L.; U.S. Patent 3,198,792; assigned to North American Philips Company, Inc.
logP3.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00486 mg/mLALOGPS
logP3.27ALOGPS
logP3.79ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)19.29ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity93.82 m3·mol-1ChemAxon
Polarizability36.39 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.982
Caco-2 permeable+0.7724
P-glycoprotein substrateSubstrate0.5449
P-glycoprotein inhibitor IInhibitor0.8841
P-glycoprotein inhibitor IIInhibitor0.6043
Renal organic cation transporterNon-inhibitor0.6931
CYP450 2C9 substrateNon-substrate0.847
CYP450 2D6 substrateNon-substrate0.8795
CYP450 3A4 substrateSubstrate0.7408
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9533
CYP450 2C19 inhibitorNon-inhibitor0.6514
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8203
Ames testNon AMES toxic0.9626
CarcinogenicityNon-carcinogens0.9151
BiodegradationNot ready biodegradable0.9575
Rat acute toxicity1.8041 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7451
hERG inhibition (predictor II)Non-inhibitor0.7454
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-2920000000-7383353a3b2099383437
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-2966000000-979f386c9d37c0f83d8c

Taxonomy

Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 3-oxosteroids / Cyclohexenones / Organic oxides / Hydrocarbon derivatives
Substituents
Progestogin-skeleton / 20-oxosteroid / Oxosteroid / 3-oxosteroid / Cyclohexenone / Cyclic ketone / Ketone / Organic oxygen compound / Organic oxide / Hydrocarbon derivative
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
3-oxo steroid, 3-oxo Delta(4)-steroid, 20-oxo steroid (CHEBI:31527)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Blois SM, Joachim R, Kandil J, Margni R, Tometten M, Klapp BF, Arck PC: Depletion of CD8+ cells abolishes the pregnancy protective effect of progesterone substitution with dydrogesterone in mice by altering the Th1/Th2 cytokine profile. J Immunol. 2004 May 15;172(10):5893-9. [PubMed:15128769]
  2. Tamaya T, Tsurusaki T, Ide N, Yamada T, Murakami T, Wada K, Fujimoto Z, Okada H: Nuclear translocation of progesterone receptor--progestogen complex in vitro. Nihon Sanka Fujinka Gakkai Zasshi. 1983 Jan;35(1):77-82. [PubMed:6827166]
  3. Raghupathy R, Al Mutawa E, Makhseed M, Azizieh F, Szekeres-Bartho J: Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage. BJOG. 2005 Aug;112(8):1096-101. [PubMed:16045524]
  4. Okada H: [Metabolism, structure and biological activity of sex steroids]. Nihon Naibunpi Gakkai Zasshi. 1993 Feb 20;69(2):67-79. [PubMed:8486204]
  5. Tamaya T, Furuta N, Ohono Y, Ide N, Tsurusaki T, Okada H: Chromatin transcription by progesterone-receptor complex in rabbit uterus. Endocrinol Jpn. 1979 Feb;26(1):117-22. [PubMed:436795]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:36