Identification

Name
Equilin
Accession Number
DB02187  (EXPT01355)
Type
Small Molecule
Groups
Experimental
Description

An estrogenic steroid produced by horses. It has a total of four double bonds in the A- and B-ring. High concentration of euilin is found in the urine of pregnant mares. [PubChem]

Equilin is one of the estrogens present in the mixture of estrogens isolated from horse urine and marketed as Premarin. Premarin became the most commonly used form of estrogen for hormone replacement therapy in the United States of America. Estrone is the major estrogen in Premarin (about 50%) and equilin is present as about 25% of the total. Estrone is a major estrogen that is normally found in women. Equilin is not normally present in women, so there has been interest in the effects of equilin on the human body. [Wikipedia]

The estrogens in Premarin are present mainly as "conjugates", modified chemical forms in which the active estrogen is coupled to another chemical group such as sulfate. Estrone sulfate is usually the major form of estrogen in women. After being taken into a woman's body, the conjugated estrogens of Premarin are converted to the active unconjugated estrogens or excreted from the woman's body. Estrone can be converted to estradiol, which is thought to be the major active estrogen in women. [Wikipedia]

Structure
Thumb
Synonyms
  • 1,3,5,7-Estratetraen-3-ol-17-one
  • 7-Dehydroestrone
  • Dihydroequilenin
  • Equilin
Categories
UNII
08O86EX0J4
CAS number
474-86-2
Weight
Average: 268.3502
Monoisotopic: 268.146329884
Chemical Formula
C18H20O2
InChI Key
WKRLQDKEXYKHJB-HFTRVMKXSA-N
InChI
InChI=1S/C18H20O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3-5,10,14,16,19H,2,6-9H2,1H3/t14-,16+,18+/m1/s1
IUPAC Name
(1S,11S,15S)-5-hydroxy-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2(7),3,5,9-tetraen-14-one
SMILES
[H][C@@]12CCC(=O)[C@@]1(C)CC[C@]1([H])C3=C(CC=C21)C=C(O)C=C3

Pharmacology

Indication

For the treatment of moderate to severe vasomotor symptoms associated with the menopause, atrophic vaginitis, osteoporosis, hypoestrogenism due to hypogonadism, castration, primary ovarian failure, breast cancer (for palliation only), and Advanced androgen-dependent carcinoma of the prostate (for palliation only)

Pharmacodynamics

Equilin is a component of Premarin (conjugated estrogens), a mixture of the water soluble salts of sulfate esters from estrone, equilin, 17 alpha-dihydroequilin, and other related steroids, may be derived from pregnant equine urine or yam and soy plants. Estrogens are important in the development and maintenance of the female reproductive system and secondary sex characteristics. They promote growth and development of the vagina, uterus, and fallopian tubes, and enlargement of the breasts. Indirectly, they contribute to the shaping of the skeleton, maintenance of tone and elasticity of urogenital structures, changes in the epiphyses of the long bones that allow for the pubertal growth spurt and its termination, growth of axillary and pubic hair, and pigmentation of the nipples and genitals. Decline of estrogenic activity at the end of the menstrual cycle can bring on menstruation, although the cessation of progesterone secretion is the most important factor in the mature ovulatory cycle. However, in the preovulatory or nonovulatory cycle, estrogen is the primary determinant in the onset of menstruation. Estrogens also affect the release of pituitary gonadotropins. The pharmacologic effects of conjugated estrogens are similar to those of endogenous estrogens.

Mechanism of action

Estrogens enter the cells of responsive tissues (e.g., female organs, breasts, hypothalamus, pituitary) where they interact with a protein receptor, subsequently increasing the rate of synthesis of DNA, RNA, and some proteins. Estrogens decrease the secretion of gonadotropin-releasing hormone by the hypothalamus, reducing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary.

TargetActionsOrganism
UEstradiol 17-beta-dehydrogenase 1Not AvailableHuman
UEstrogen receptor alphaNot AvailableHuman
Absorption

Well absorbed.

Volume of distribution
Not Available
Protein binding

90% bound to plasma proteins

Metabolism

Hepatic

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Equilin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Equilin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Equilin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Equilin.
5-androstenedioneThe metabolism of Equilin can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Equilin can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Equilin.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Equilin.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Equilin.
AcalabrutinibThe metabolism of Equilin can be decreased when combined with Acalabrutinib.
Food Interactions
Not Available

References

General References
  1. Sawicki MW, Erman M, Puranen T, Vihko P, Ghosh D: Structure of the ternary complex of human 17beta-hydroxysteroid dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin) and NADP+. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):840-5. [PubMed:9927655]
External Links
KEGG Drug
D04041
KEGG Compound
C14392
PubChem Compound
223368
PubChem Substance
46506633
ChemSpider
193995
BindingDB
50423544
ChEBI
42309
ChEMBL
CHEMBL323533
HET
EQI
Wikipedia
Equilin
PDB Entries
1equ

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)239 °CPhysProp
water solubility1.41 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
Predicted Properties
PropertyValueSource
Water Solubility0.0133 mg/mLALOGPS
logP3.8ALOGPS
logP3.9ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.41ChemAxon
pKa (Strongest Basic)-6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.93 m3·mol-1ChemAxon
Polarizability30.55 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+0.9192
Caco-2 permeable+0.875
P-glycoprotein substrateSubstrate0.6807
P-glycoprotein inhibitor INon-inhibitor0.8085
P-glycoprotein inhibitor IINon-inhibitor0.8881
Renal organic cation transporterNon-inhibitor0.6704
CYP450 2C9 substrateNon-substrate0.7245
CYP450 2D6 substrateNon-substrate0.9081
CYP450 3A4 substrateSubstrate0.7666
CYP450 1A2 substrateInhibitor0.9108
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8209
CYP450 3A4 inhibitorNon-inhibitor0.8156
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5528
Ames testNon AMES toxic0.9109
CarcinogenicityNon-carcinogens0.93
BiodegradationNot ready biodegradable0.9319
Rat acute toxicity1.8021 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7619
hERG inhibition (predictor II)Non-inhibitor0.601
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
Mass Spectrum (Electron Ionization)MSsplash10-014i-3940000000-b80393e552aa78600070
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
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as oxosteroids. These are steroid derivatives carrying a C=O group attached to steroid skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Oxosteroids
Direct Parent
Oxosteroids
Alternative Parents
3-hydroxy delta-7-steroids / 17-oxosteroids / Delta-7-steroids / Phenanthrenes and derivatives / Naphthalenes / 1-hydroxy-2-unsubstituted benzenoids / Ketones / Organic oxides / Hydrocarbon derivatives
Substituents
3-hydroxy-delta-7-steroid / 3-hydroxysteroid / Hydroxysteroid / Oxosteroid / 17-oxosteroid / Delta-7-steroid / Phenanthrene / Naphthalene / 1-hydroxy-2-unsubstituted benzenoid / Benzenoid
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
17-oxo steroid, 3-hydroxy steroid (CHEBI:42309) / Estrane and derivatives (C14392) / C18 steroids (estrogens) and derivatives (LMST02010026)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Testosterone dehydrogenase (nad+) activity
Specific Function
Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
Gene Name
HSD17B1
Uniprot ID
P14061
Uniprot Name
Estradiol 17-beta-dehydrogenase 1
Molecular Weight
34949.715 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Starcevic S, Brozic P, Turk S, Cesar J, Rizner TL, Gobec S: Synthesis and biological evaluation of (6- and 7-phenyl) coumarin derivatives as selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1. J Med Chem. 2011 Jan 13;54(1):248-61. doi: 10.1021/jm101104z. Epub 2010 Dec 7. [PubMed:21138273]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
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

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 05:13