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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GroupsApproved, Withdrawn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 Identifiers 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
SaltsNot Available
Categories
UNII90I02KLE8K
CAS number152-62-5
WeightAverage: 312.4458
Monoisotopic: 312.20893014
Chemical FormulaC21H28O2
InChI KeyInChIKey=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
[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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassPregnane steroids
Direct ParentGluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
Substituents
  • Progestogin-skeleton
  • 20-oxosteroid
  • Oxosteroid
  • 3-oxosteroid
  • Cyclic ketone
  • Ketone
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed 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.
PharmacodynamicsDydrogesterone 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 actionDydrogesterone 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.
Related Articles
AbsorptionRapidly 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 lifeDydrogesterone: 5-7 hours, 20-dihydrodydrogesterone (DHD) metabolite: 14-17 hours
ClearanceNot Available
ToxicityNo 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
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Solvay pharmaceuticals
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point168-169Reerink, 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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot 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 CodesG03DB01G03FA14G03FB08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be decreased when used in combination with Dydrogesterone.
ApixabanThe therapeutic efficacy of Apixaban can be decreased when used in combination with Dydrogesterone.
ArgatrobanThe therapeutic efficacy of Argatroban can be decreased when used in combination with Dydrogesterone.
BivalirudinThe therapeutic efficacy of Bivalirudin can be decreased when used in combination with Dydrogesterone.
Dabigatran etexilateThe therapeutic efficacy of Dabigatran etexilate can be decreased when used in combination with Dydrogesterone.
DalteparinThe therapeutic efficacy of Dalteparin can be decreased when used in combination with Dydrogesterone.
DanaparoidThe therapeutic efficacy of Danaparoid can be decreased when used in combination with Dydrogesterone.
DesirudinThe therapeutic efficacy of Desirudin can be decreased when used in combination with Dydrogesterone.
EdoxabanThe therapeutic efficacy of Edoxaban can be decreased when used in combination with Dydrogesterone.
EnoxaparinThe therapeutic efficacy of Enoxaparin can be decreased when used in combination with Dydrogesterone.
Fondaparinux sodiumThe therapeutic efficacy of Fondaparinux sodium can be decreased when used in combination with Dydrogesterone.
HeparinThe therapeutic efficacy of Heparin can be decreased when used in combination with Dydrogesterone.
NadroparinThe therapeutic efficacy of Nadroparin can be decreased when used in combination with Dydrogesterone.
RivaroxabanThe therapeutic efficacy of Rivaroxaban can be decreased when used in combination with Dydrogesterone.
TinzaparinThe therapeutic efficacy of Tinzaparin can be decreased when used in combination with Dydrogesterone.
UlipristalThe therapeutic efficacy of Dydrogesterone can be decreased when used in combination with Ulipristal.
WarfarinThe therapeutic efficacy of Warfarin can be decreased when used in combination with Dydrogesterone.
Food InteractionsNot Available

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 ]
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Drug created on June 13, 2005 07:24 / Updated on April 15, 2014 17:22