Identification

Name
Ethinylestradiol
Accession Number
DB00977  (APRD00691)
Type
Small Molecule
Groups
Approved
Description

A semisynthetic alkylated estradiol with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally and is often used as the estrogenic component in oral contraceptives. Ethinyl estradiol is marketed mostly as a combination oral contraceptive under several brand names such as Alesse, Tri-Cyclen, Triphasil, and Yasmin. The FDA label includes a black box warning that states that combination oral contraceptives should not be used in women over 35 years old who smoke due to the increased risk of serious cardiovascular side effects.

Structure
Thumb
Synonyms
  • 17-ethinyl-3,17-estradiol
  • 17-ethinyl-3,17-oestradiol
  • 17-ethinylestradiol
  • 17alpha-Ethinyl estradiol
  • 17α-ethynylestradiol
  • Ethinyl estradiol
  • Ethinylestradiolum
  • Ethinyloestradiol
  • Ethynyl estradiol
  • Etinilestradiol
External IDs
NSC-10973
Active Moieties
NameKindUNIICASInChI Key
Estradiolunknown4TI98Z838E50-28-2VOXZDWNPVJITMN-ZBRFXRBCSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Estinyl Tab 0.05mgTablet.05 mgOralSchering Plough1951-12-312000-07-11Canada
Estinyl Tab 0.5mgTablet.5 mgOralSchering Plough1951-12-312000-07-11Canada
Estinyl Tablets 0.02 Mg.Tablet.02 mgOralSchering Plough1951-12-311998-11-17Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AfirmelleEthinylestradiol (0.02 mg/1) + Levonorgestrel (0.1 mg/1)KitAurobindo Pharma2016-11-14Not applicableUs
Alesse 21Ethinylestradiol (20 mcg) + Levonorgestrel (100 mcg)TabletOralPfizer1998-01-07Not applicableCanada
Alesse 28Ethinylestradiol (20 mcg) + Levonorgestrel (100 mcg)TabletOralPfizer1998-01-07Not applicableCanada
Alesse 28Ethinylestradiol (0.02 mg/1) + Levonorgestrel (0.1 mg/1)KitWyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.1997-04-012008-02-29Us
AltaveraEthinylestradiol (0.03 mg/1) + Levonorgestrel (0.15 mg/1)KitSandoz2010-08-03Not applicableUs
AltaveraEthinylestradiol (0.03 mg/1) + Levonorgestrel (0.15 mg/1)KitXiromed, Llc.2018-01-01Not applicableUs
Alyacen 1/35Ethinylestradiol (0.035 mg/1) + Norethisterone (1 mg/1)KitGlenmark Pharmaceuticals Inc.,Usa2012-01-19Not applicableUs
Alyacen 1/35Ethinylestradiol (0.035 mg/1) + Norethisterone (1 mg/1)KitRemedy Repack2018-05-16Not applicableUs
Alyacen 1/35Ethinylestradiol (0.035 mg/1) + Norethisterone (1 mg/1)KitA-S Medication Solutions2012-01-19Not applicableUs
Alyacen 7/7/7Ethinylestradiol (0.035 mg/1) + Ethinylestradiol (0.035 mg/1) + Ethinylestradiol (0.035 mg/1) + Norethisterone (0.5 mg/1) + Norethisterone (0.75 mg/1) + Norethisterone (1 mg/1)KitGlenmark Pharmaceuticals Inc.,Usa2012-01-19Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
FalessaEthinylestradiol (0.02 mg/1) + Folic Acid (1 mg/1) + Levonorgestrel (0.1 mg/1)KitAvion Pharmaceuticals, Llc2014-02-17Not applicableUs
International/Other Brands
Estinyl (Schering)
Categories
UNII
423D2T571U
CAS number
57-63-6
Weight
Average: 296.4034
Monoisotopic: 296.177630012
Chemical Formula
C20H24O2
InChI Key
BFPYWIDHMRZLRN-SLHNCBLASA-N
InChI
InChI=1S/C20H24O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,5,7,12,16-18,21-22H,4,6,8-11H2,2H3/t16-,17-,18+,19+,20+/m1/s1
IUPAC Name
(1S,10R,11S,14R,15S)-14-ethynyl-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2(7),3,5-triene-5,14-diol
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3

Pharmacology

Indication

For treatment of moderate to severe vasomotor symptoms associated with the menopause, female hypogonadism, prostatic carcinoma-palliative therapy of advanced disease, breast cancer, as an oral contraceptive, and as emergency contraceptive.

Associated Conditions
Associated Therapies
Pharmacodynamics

Ethinyl estradiol is a synthetic derivative of the natural estrogen estradiol. It is one of two estrogens currently used in oral contraceptive pills. The other, mestranol, is converted to ethinyl estradiol before it is biologically active. Ethinyl estradiol and norethindrone are used together as an oral contraceptive agent.

Mechanism of action

Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. This cascade is initiated by initially binding to the estrogen receptors. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

TargetActionsOrganism
AEstrogen receptor alpha
agonist
Human
UNuclear receptor subfamily 1 group I member 2
agonist
Human
USex hormone-binding globulinNot AvailableHuman
Absorption

Rapid and complete absorption follows oral intake of ethinyl estradiol (bioavailability 43%).

Volume of distribution
Not Available
Protein binding

97%

Metabolism

Hepatic. Quantitatively, the major metabolic pathway for ethinyl estradiol, both in rats and in humans, is aromatic hydroxylation, as it is for the natural estrogens.

Route of elimination
Not Available
Half life

36 +/- 13 hours

Clearance
Not Available
Toxicity

Oral, mouse LD50: 1737 mg/kg. Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females. The FDA label includes a black box warning that states that combination oral contraceptives with ethinyl estradiol should not be used in women over 35 years old who smoke due to the increased risk of serious cardiovascular side effects.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinEthinyl Estradiol may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinEthinyl Estradiol may decrease the anticoagulant activities of (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Ethinyl Estradiol.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Ethinyl Estradiol.
4-hydroxycoumarinEthinyl Estradiol may decrease the anticoagulant activities of 4-hydroxycoumarin.
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Ethinyl Estradiol.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Ethinyl Estradiol.
AbciximabEthinyl Estradiol may decrease the anticoagulant activities of Abciximab.
AbemaciclibThe serum concentration of Ethinyl Estradiol can be increased when it is combined with Abemaciclib.
AbirateroneThe serum concentration of Ethinyl Estradiol can be increased when it is combined with Abiraterone.
Food Interactions
Not Available

References

Synthesis Reference

Andreas Sachse, "Method of female hormonal contraception using a fixed extended cycle hormonal preparation containing dienogest and ethinyl estradiol." U.S. Patent US20060079491, issued April 13, 2006.

US20060079491
General References
Not Available
External Links
Human Metabolome Database
HMDB0001926
KEGG Drug
D00554
KEGG Compound
C07534
PubChem Compound
5991
PubChem Substance
46508618
ChemSpider
5770
BindingDB
50187243
ChEBI
4903
ChEMBL
CHEMBL691
Therapeutic Targets Database
DAP001018
PharmGKB
PA449527
HET
3WF
RxList
RxList Drug Page
Wikipedia
Ethinylestradiol
ATC Codes
G03AA03 — Lynestrenol and ethinylestradiolG03AA04 — Megestrol and ethinylestradiolG03AB07 — Chlormadinone and ethinylestradiolG03AA08 — Medroxyprogesterone and ethinylestradiolG03AA10 — Gestodene and ethinylestradiolG03AB05 — Desogestrel and ethinylestradiolG03AA09 — Desogestrel and ethinylestradiolG03AB01 — Megestrol and ethinylestradiolG03AA11 — Norgestimate and ethinylestradiolL02AA03 — EthinylestradiolG03CA01 — EthinylestradiolG03AB03 — Levonorgestrel and ethinylestradiolG03AB02 — Lynestrenol and ethinylestradiolG03AA05 — Norethisterone and ethinylestradiolG03AA07 — Levonorgestrel and ethinylestradiolG03AA12 — Drospirenone and ethinylestradiolG03AA01 — Etynodiol and ethinylestradiolG03AA02 — Quingestanol and ethinylestradiolG03AA16 — Dienogest and ethinylestradiolG03AA13 — Norelgestromin and ethinylestradiolG03AB06 — Gestodene and ethinylestradiolG03AB04 — Norethisterone and ethinylestradiolG03AA15 — Chlormadinone and ethinylestradiolG03AA06 — Norgestrel and ethinylestradiol
AHFS Codes
  • 68:16.04 — Estrogens
PDB Entries
4x1f / 4x1g
FDA label
Download (470 KB)
MSDS
Download (73.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingSupportive CareEndometriosis of Uterus1
1CompletedNot AvailableBioequivalence1
1CompletedNot AvailableChronic Hepatitis C Virus (HCV) Infection1
1CompletedNot AvailableHealthy Volunteers4
1CompletedNot AvailableHepatitis C Viral Infection1
1CompletedNot AvailableHepatitis C Virus (HCV)1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections2
1CompletedNot AvailablePharmacokinetics1
1CompletedBasic ScienceFollicle Count / Follicle Size / Induction of follicle development / Oral Contraceptives (OC) / Ovarian Follicle1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceHealthy Volunteers / Pharmacokinetics of Mirabegron1
1CompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1CompletedOtherHealthy Female Volunteers / Type 2 Diabetes Mellitus1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentArthritic Psoriasis / Inflammatory Bowel Diseases (IBD) / Psoriasis / Systemic Lupus Erythematosus (SLE)1
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
1CompletedTreatmentContraception2
1CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
1CompletedTreatmentDrug Interactions1
1CompletedTreatmentHealthy Volunteers5
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1CompletedTreatmentRheumatoid Arthritis1
1CompletedTreatmentType 2 Diabetes Mellitus2
1Not Yet RecruitingBasic ScienceMalignancies, Hematologic1
1RecruitingBasic ScienceHealthy Females1
1RecruitingOtherHealthy Females1
1RecruitingOtherHealthy Volunteers1
1RecruitingPreventionContraception1
1RecruitingTreatmentTumors, Solid1
1TerminatedNot AvailableCystic Fibrosis Exacerbations While on and Off Hormonal Contraception1
1TerminatedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
1TerminatedHealth Services ResearchHuman Immunodeficiency Virus (HIV)1
1TerminatedTreatmentHealthy Volunteers1
1Unknown StatusTreatmentPolycystic Ovaries Syndrome1
1WithdrawnBasic ScienceHealthy Volunteers1
1, 2CompletedPreventionContraception / Hemostasis Parameter / Liver Metabolism1
2Active Not RecruitingTreatmentPolycystic Ovarian Syndrome1
2CompletedBasic ScienceHemostasis / Oral Contraceptives (OC)2
2CompletedPreventionBreakthrough Bleeding1
2CompletedPreventionContraception2
2CompletedPreventionEndometrial Cancers1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1
2CompletedPreventionMigraines1
2CompletedPreventionPrevention of Pregnancy1
2CompletedTreatmentBone Mineral Density1
2CompletedTreatmentContraception1
2CompletedTreatmentContraception / Ovulation Inhibition1
2CompletedTreatmentDysmenorrhea1
2CompletedTreatmentOral Contraceptives (OC)1
2CompletedTreatmentOvulation1
2CompletedTreatmentOvulation Suppression1
2Not Yet RecruitingTreatmentRett's Syndrome1
2RecruitingTreatmentAnorexia Nervosa (AN)1
2RecruitingTreatmentPolycystic Ovarian Syndrome1
2TerminatedTreatmentContraception / Ovulation Inhibition1
2TerminatedTreatmentDepression / PMDD / Premenstrual Dysphoric Disorder / Premenstrual Syndrome1
2TerminatedTreatmentHidradenitis Suppurativa (HS)1
2Unknown StatusTreatmentContraception1
2, 3CompletedTreatmentFailed Induction of Labor1
3Active Not RecruitingTreatmentContraception1
3CompletedEducational/Counseling/TrainingOral Contraceptives (OC)1
3CompletedPreventionContraception12
3CompletedPreventionContraception / Neural Tube Defects (NTDs) / Oral Contraceptives (OC)1
3CompletedPreventionContraception / Oral Contraceptives (OC) / Ovulation Inhibition1
3CompletedPreventionPregnancy Prevention1
3CompletedTreatmentAcne Vulgaris4
3CompletedTreatmentContraception1
3CompletedTreatmentContraception: Optional Applicator for Insertion of Vaginal Ring1
3CompletedTreatmentDysmenorrhea1
3CompletedTreatmentHealthy Volunteers5
3CompletedTreatmentOral Contraceptives (OC)1
3CompletedTreatmentPolycystic Ovaries Syndrome2
3CompletedTreatmentPremenstrual Dysphoric Disorder ( PMDD)1
3CompletedTreatmentPremenstrual Syndrome1
3CompletedTreatmentPrimary Dysmenorrhoea1
3CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
3CompletedTreatmentTurner's Syndrome1
3RecruitingTreatmentBladder Cancers / Transitional Cell Carcinoma / Ureteral Cancer1
3RecruitingTreatmentExercise-related Amenorrhea1
3RecruitingTreatmentPrimary Ovarian Insufficiency1
3TerminatedPreventionContraception1
3TerminatedTreatmentCancer, Breast1
3Unknown StatusNot AvailableContraceptive Affecting Blood Pressure / Contraceptive Affecting the Autonomic Nervous System1
3Unknown StatusTreatmentOral Contraceptives (OC)1
3WithdrawnNot AvailableMetrorrhagia1
3WithdrawnTreatmentOsteopenia1
4Active Not RecruitingBasic ScienceBone; Disorder, Development and Growth1
4Active Not RecruitingBasic ScienceOther Disorders of Bone Development and Growth1
4Active Not RecruitingPreventionBacterial Vaginosis (BV) / Human Immunodeficiency Virus (HIV)1
4CompletedBasic ScienceAdverse Effect of Oral Contraceptives, Subsequent Encounter1
4CompletedBasic ScienceContraception2
4CompletedDiagnosticBody Weights / Contraceptive Usage1
4CompletedPreventionBMI >30 kg/m2 / Cardiovascular Disease (CVD) / Insulin Resistance / Metabolic Syndromes1
4CompletedPreventionContraception1
4CompletedScreeningCardiovascular Risks / Insulin Sensitivity / Perimenopausal Disorder1
4CompletedTreatmentContraception2
4CompletedTreatmentContraception / Menopause / Quality of Life1
4CompletedTreatmentEmergency Contraception1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentInfertilities2
4CompletedTreatmentPolycystic Ovaries Syndrome3
4CompletedTreatmentPremature Ovarian Failure (POF)1
4CompletedTreatmentPremenstrual Dysphoric Disorder1
4CompletedTreatmentPremenstrual Syndrome1
4CompletedTreatmentPrimary Dysmenorrhoea1
4Enrolling by InvitationTreatmentBody Weight Changes1
4Not Yet RecruitingPreventionEmergency Contraception / Healthy, Reproductive Age Women1
4RecruitingPreventionBacterial Vaginosis (BV)1
4RecruitingTreatmentContraception / Human Immunodeficiency Virus (HIV)1
4RecruitingTreatmentDysmenorrhea / Endometriosis / Interstitial Cystitis / Migraine Disorders / Pain, Chronic / Pelvic Pain / Visceral Pain1
4TerminatedNot AvailableInfertilities1
4TerminatedScreeningContraception / Hypercoagulability1
4TerminatedTreatmentAbnormal Uterine Bleeding, Unspecified / Uterine Bleeding Heavy1
4Unknown StatusNot AvailableDysmenorrhea / Endometriotic Cysts / Painful Intercourse / Pelvic Pain1
4Unknown StatusPreventionHyperandrogenism / Menstrual Irregularities / Polycystic Ovarian Syndrome1
4Unknown StatusTreatmentBacterial Vaginosis (BV)1
4Unknown StatusTreatmentContraceptive Methods Comparison1
4Unknown StatusTreatmentMenstrual Problem1
4WithdrawnTreatmentInfertilities1
Not AvailableActive Not RecruitingNot AvailableContraception / Human Immunodeficiency Virus (HIV) / Immune Cells (Mucosal and Systemic)1
Not AvailableActive Not RecruitingNot AvailableDysmenorrhea1
Not AvailableActive Not RecruitingTreatmentEndometriosis / Infertilities1
Not AvailableCompletedNot AvailableAcne Vulgaris2
Not AvailableCompletedNot AvailableAcne / Contraception / Premenstrual Syndrome1
Not AvailableCompletedNot AvailableContraception4
Not AvailableCompletedNot AvailableContraceptive Usage / Vaginal Epithelial Disruption1
Not AvailableCompletedNot AvailableHormonal Contraception1
Not AvailableCompletedNot AvailableMetabolic Syndromes / Polycystic Ovaries Syndrome1
Not AvailableCompletedNot AvailablePharmacokinetics1
Not AvailableCompletedBasic ScienceCoronary Heart Disease (CHD)1
Not AvailableCompletedHealth Services ResearchOvarian Follicle1
Not AvailableCompletedTreatmentContraception1
Not AvailableCompletedTreatmentDepression / Premenstrual Syndrome1
Not AvailableCompletedTreatmentEmotional / Headaches / Pelvic Pain1
Not AvailableCompletedTreatmentHealthy Volunteers1
Not AvailableCompletedTreatmentHypermenorrhea1
Not AvailableCompletedTreatmentInsulin Resistance / Polycystic Ovaries Syndrome1
Not AvailableCompletedTreatmentSystemic Lupus Erythematosus (SLE)1
Not AvailableCompletedTreatmentTemporomandibular Joint Disorders1
Not AvailableCompletedTreatmentThrombosis, Venous1
Not AvailableNot Yet RecruitingTreatmentPremature Menopause / Primary Ovarian Insufficiency1
Not AvailableRecruitingNot AvailableInfertilities1
Not AvailableRecruitingBasic ScienceCystic Fibrosis (CF)1
Not AvailableRecruitingTreatmentHyperandrogenism / Metabolic Cardiovascular Syndrome1
Not AvailableTerminatedBasic ScienceContraception1
Not AvailableTerminatedPreventionAdolescents Seeking Contraception / Contraception Desired1
Not AvailableTerminatedTreatmentIn-Vitro Fertilization / Infertilities1
Not AvailableUnknown StatusBasic ScienceOral Contraceptives (OC)1
Not AvailableUnknown StatusTreatmentEndothelial Dysfunction / Polycystic Ovaries Syndrome1
Not AvailableUnknown StatusTreatmentFemale Contraception1
Not AvailableWithdrawnTreatmentDysmenorrhea / Menstruation Disorders / Menstruation Disturbances1

Pharmacoeconomics

Manufacturers
  • Schering corp sub schering plough corp
  • Pharmacia and upjohn co
  • Organon usa inc
Packagers
  • Amerisource Health Services Corp.
  • Barr Pharmaceuticals
  • Bayer Healthcare
  • Dept Health Central Pharmacy
  • Duramed
  • Mckesson Corp.
  • NV Organon
  • Organon Pharmaceuticals
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Prasco Labs
  • Schering Corp.
  • Spectrum Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
Kit
TabletOral
TabletOral.05 mg
TabletOral.5 mg
TabletOral.02 mg
Patch, extended releaseTransdermal
Tablet, film coatedOral
Tablet, chewableOral
Insert, extended releaseVaginal
RingVaginal
PatchTransdermal
KitOral
Prices
Unit descriptionCostUnit
Ethinyl estradiol powder140.0USD g
Ortho-Cyclen (28) 28 0.25-35 mg-mcg tablet Disp Pack38.99USD disp
Ortho tri-cyclen lo tablet2.68USD tablet
Ortho-cyclen 28 tablet1.13USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6156742No2000-12-052020-12-05Us
US6787531No2000-08-312020-08-31Us
US6933395No1997-08-112017-08-11Us
US5876746No1995-11-202015-11-20Us
US5989581No1998-04-082018-04-08Us
US6214815Yes1999-12-092019-12-09Us
US6667050No1999-04-062019-04-06Us
US5898032No1997-06-232017-06-23Us
USRE39861No1997-06-232017-06-23Us
US6987101No1997-12-222017-12-22Us
US7163931No2001-12-202021-12-20Us
US6958326No2001-12-202021-12-20Us
US5798338No1995-07-102015-07-10Us
US7320969No2004-01-302024-01-30Us
US7615545No2003-06-152023-06-15Us
US7855190No2008-12-052028-12-05Us
US7858605No2003-06-232023-06-23Us
US6500814No1998-09-032018-09-03Us
US7704984No2009-02-022029-02-02Us
US6441168No2002-07-302022-07-30Us
US8617597No2010-02-082030-02-08Us
US8450299No2005-10-072025-10-07Us
US8415332No2009-03-112029-03-11Us
US6652880No2000-03-292020-03-29Us
US6716814No2001-08-162021-08-16Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)142-144Inhoffen, H.H. and Hohlweg, W.; U.S. Patent 2,265,976; December 9, 1941; assigned to Schering Corp.
water solubility11.3 mg/L (at 27 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.67HANSCH,C ET AL. (1995)
logS-4.3ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.00677 mg/mLALOGPS
logP3.63ALOGPS
logP3.9ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)10.33ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity87.37 m3·mol-1ChemAxon
Polarizability34.53 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9965
Blood Brain Barrier+0.8546
Caco-2 permeable+0.8638
P-glycoprotein substrateSubstrate0.6892
P-glycoprotein inhibitor INon-inhibitor0.9006
P-glycoprotein inhibitor IINon-inhibitor0.9449
Renal organic cation transporterNon-inhibitor0.84
CYP450 2C9 substrateNon-substrate0.7178
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.715
CYP450 1A2 substrateInhibitor0.8941
CYP450 2C9 inhibitorNon-inhibitor0.9186
CYP450 2D6 inhibitorNon-inhibitor0.9506
CYP450 2C19 inhibitorNon-inhibitor0.6641
CYP450 3A4 inhibitorInhibitor0.5224
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6776
Ames testNon AMES toxic0.9155
CarcinogenicityNon-carcinogens0.8519
BiodegradationNot ready biodegradable0.9879
Rat acute toxicity2.4584 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8805
hERG inhibition (predictor II)Inhibitor0.5788
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.42 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-03di-0890000000-5219bc8ac1212313c9c0
Mass Spectrum (Electron Ionization)MSsplash10-03dj-2980000000-831c8190c59f98fc8623
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-000b-0290000000-0ef72fb5e00440b9ff50
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-000i-0960000000-945d82a0ab94f246ac88
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-056s-2910000000-0d38daebb87a39304e91
MS/MS Spectrum - EI-B (HITACHI M-80) , PositiveLC-MS/MSsplash10-03di-0890000000-7a166e952207cf7bc1d3
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
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Estrane steroids
Direct Parent
Estrogens and derivatives
Alternative Parents
3-hydroxysteroids / 17-hydroxysteroids / Phenanthrenes and derivatives / Tetralins / 1-hydroxy-2-unsubstituted benzenoids / Ynones / Tertiary alcohols / Cyclic alcohols and derivatives / Acetylides / Hydrocarbon derivatives
Substituents
Estrogen-skeleton / 3-hydroxysteroid / Hydroxysteroid / 17-hydroxysteroid / Phenanthrene / Tetralin / 1-hydroxy-2-unsubstituted benzenoid / Benzenoid / Ynone / Cyclic alcohol
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
terminal acetylenic compound, 17-hydroxy steroid, 3-hydroxy steroid (CHEBI:4903) / C18 steroids (estrogens) and derivatives (C07534) / C18 steroids (estrogens) and derivatives (LMST02010036)

Targets

Details
1. Estrogen receptor alpha
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Micevych PE, Chaban V, Ogi J, Dewing P, Lu JK, Sinchak K: Estradiol stimulates progesterone synthesis in hypothalamic astrocyte cultures. Endocrinology. 2007 Feb;148(2):782-9. Epub 2006 Nov 9. [PubMed:17095591]
  2. Garcia-Segura LM, Sanz A, Mendez P: Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection. Neuroendocrinology. 2006;84(4):275-9. Epub 2006 Nov 23. [PubMed:17124377]
  3. Brama M, Gnessi L, Basciani S, Cerulli N, Politi L, Spera G, Mariani S, Cherubini S, Scotto d'Abusco A, Scandurra R, Migliaccio S: Cadmium induces mitogenic signaling in breast cancer cell by an ERalpha-dependent mechanism. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):102-8. Epub 2006 Nov 27. [PubMed:17125913]
  4. Lehnes K, Winder AD, Alfonso C, Kasid N, Simoneaux M, Summe H, Morgan E, Iann MC, Duncan J, Eagan M, Tavaluc R, Evans CH Jr, Russell R, Wang A, Hu F, Stoica A: The effect of estradiol on in vivo tumorigenesis is modulated by the human epidermal growth factor receptor 2/phosphatidylinositol 3-kinase/Akt1 pathway. Endocrinology. 2007 Mar;148(3):1171-80. Epub 2006 Nov 30. [PubMed:17138652]
  5. Mukai H, Tsurugizawa T, Ogiue-Ikeda M, Murakami G, Hojo Y, Ishii H, Kimoto T, Kawato S: Local neurosteroid production in the hippocampus: influence on synaptic plasticity of memory. Neuroendocrinology. 2006;84(4):255-63. Epub 2006 Dec 1. [PubMed:17142999]
  6. Notch EG, Mayer GD: 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8. doi: 10.1016/j.aquatox.2009.01.001. Epub 2009 Jan 23. [PubMed:19237207]
  7. Bennink HJ: Reprint of Are all estrogens the same? Maturitas. 2008 Sep-Oct;61(1-2):195-201. [PubMed:19434891]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Xue Y, Moore LB, Orans J, Peng L, Bencharit S, Kliewer SA, Redinbo MR: Crystal structure of the pregnane X receptor-estradiol complex provides insights into endobiotic recognition. Mol Endocrinol. 2007 May;21(5):1028-38. Epub 2007 Feb 27. [PubMed:17327420]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [PubMed:25349334]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wang B, Sanchez RI, Franklin RB, Evans DC, Huskey SE: The involvement of CYP3A4 and CYP2C9 in the metabolism of 17 alpha-ethinylestradiol. Drug Metab Dispos. 2004 Nov;32(11):1209-12. Epub 2004 Aug 10. [PubMed:15304426]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
Estradiol trans-inhibits BSEP only after its secretion into bile canaliculi by Mrp2.
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL: Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology. 2000 Jan;118(1):163-72. [PubMed:10611165]
  2. Huang L, Smit JW, Meijer DK, Vore M: Mrp2 is essential for estradiol-17beta(beta-D-glucuronide)-induced cholestasis in rats. Hepatology. 2000 Jul;32(1):66-72. [PubMed:10869290]
  3. Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ: Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology. 2000 Feb;118(2):422-30. [PubMed:10648470]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL: Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology. 2000 Jan;118(1):163-72. [PubMed:10611165]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Kauffmann HM, Schrenk D: Sequence analysis and functional characterization of the 5'-flanking region of the rat multidrug resistance protein 2 (mrp2) gene. Biochem Biophys Res Commun. 1998 Apr 17;245(2):325-31. [PubMed:9571149]
  2. Trauner M, Arrese M, Soroka CJ, Ananthanarayanan M, Koeppel TA, Schlosser SF, Suchy FJ, Keppler D, Boyer JL: The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology. 1997 Jul;113(1):255-64. [PubMed:9207286]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Kim WY, Benet LZ: P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm Res. 2004 Jul;21(7):1284-93. [PubMed:15290871]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:32