Identification
NameDydrogesterone
Accession NumberDB00378  (APRD00941)
TypeSmall Molecule
GroupsApproved, Withdrawn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
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DabrostonAbbott
DufastonAbbott
DuphastonAbbott
TerolutSolvay
Brand mixturesNot Available
Categories
UNII90I02KLE8K
CAS number152-62-5
WeightAverage: 312.4458
Monoisotopic: 312.20893014
Chemical FormulaC21H28O2
InChI KeyJGMOKGBVKVMRFX-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
[H][C@@]12CC[[email protected]](C(C)=O)[C@@]1(C)CC[C@]1([H])[C@@]2([H])C=CC2=CC(=O)CC[C@@]12C
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Progesterone receptorProteinyes
agonist
HumanP06401 details
Related Articles
Absorption

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

Volume of distributionNot Available
Protein bindingNot Available
Metabolism

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

SubstrateEnzymesProduct
Dydrogesterone
Not Available
20-dihydrodydrogesteroneDetails
Route of eliminationNot Available
Half life

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

ClearanceNot 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
PathwaysNot 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, 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
Citric AcidThe therapeutic efficacy of Citric Acid can be decreased when used in combination with Dydrogesterone.Nutraceutical, Vet Approved
Conestat alfaDydrogesterone may increase the thrombogenic activities of C1 Esterase Inhibitor (Recombinant).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
DarexabanThe therapeutic efficacy of Ym150 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
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
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 C1 Esterase Inhibitor (Human).Approved
LepirudinThe therapeutic efficacy of Lepirudin can be decreased when used in combination with Dydrogesterone.Approved
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
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
PhenprocoumonThe therapeutic efficacy of Phenprocoumon 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
ReviparinThe therapeutic efficacy of Reviparin can be decreased when used in combination with Dydrogesterone.Approved
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
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 InteractionsNot 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
ATC CodesG03FA14 — Dydrogesterone and estrogenG03DB01 — DydrogesteroneG03FB08 — Dydrogesterone and estrogen
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3CompletedPreventionPostmenopausal Syndrome1
2, 3Not Yet RecruitingTreatmentRecurrent Miscarriages1
3Active Not RecruitingTreatmentInfertility, Female1
3CompletedPreventionPreterm Delivery1
3CompletedTreatmentInfertility, Female1
3CompletedTreatmentRecurrent Miscarriages1
3CompletedTreatmentOne to five years postmenopausal2
3RecruitingTreatmentPregnancy1
4RecruitingTreatmentRecurrent Pregnancy Losses1
Not AvailableActive Not RecruitingNot AvailableEndometriosis1
Not AvailableCompletedPreventionPremature Labour1
Not AvailableCompletedTreatmentLuteal Phase Defect1
Not AvailableCompletedTreatmentMenopausal and Postmenopausal Disorders1
Not AvailableRecruitingPreventionIntrauterine Adhesions1
Pharmacoeconomics
Manufacturers
  • Solvay pharmaceuticals
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-2920000000-7383353a3b2099383437View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-03di-2966000000-979f386c9d37c0f83d8cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
KingdomChemical entities
Super ClassOrganic compounds
ClassLipids and lipid-like molecules
Sub ClassSteroids and steroid derivatives
Direct ParentGluco/mineralocorticoids, progestogins and derivatives
Alternative Parents20-oxosteroids / 3-oxosteroids / Cyclohexenones / Organic oxides / Hydrocarbon derivatives
SubstituentsProgestogin-skeleton / 20-oxosteroid / Oxosteroid / 3-oxosteroid / Cyclohexenone / Cyclic ketone / Ketone / Organic oxygen compound / Organic oxide / Hydrocarbon derivative
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors3-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 isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial ...
Gene Name:
PGR
Uniprot ID:
P06401
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 July 18, 2017 16:48