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
Structure for Equilin (DB02187)
- 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.
Target Actions Organism UEstradiol 17-beta-dehydrogenase 1 Not Available Humans UEstrogen receptor alpha Not Available Humans - 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
Drug Interaction (R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Equilin. (S)-Warfarin The metabolism of (S)-Warfarin can be decreased when combined with Equilin. 3,5-diiodothyropropionic acid The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Equilin. 4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be decreased when combined with Equilin. 5-androstenedione The metabolism of Equilin can be decreased when combined with 5-androstenedione. 6-Deoxyerythronolide B The metabolism of Equilin can be decreased when combined with 6-Deoxyerythronolide B. 6-O-benzylguanine The metabolism of 6-O-benzylguanine can be decreased when combined with Equilin. 7-ethyl-10-hydroxycamptothecin The metabolism of Equilin can be decreased when combined with 7-ethyl-10-hydroxycamptothecin. 9-aminocamptothecin The metabolism of 9-aminocamptothecin can be decreased when combined with Equilin. Abatacept The metabolism of Equilin can be increased when combined with Abatacept. - Food Interactions
- Not Available
References
- General References
- 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
- PDB Entries
- 1equ
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 239 °C PhysProp water solubility 1.41 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) - Predicted Properties
Property Value Source Water Solubility 0.0133 mg/mL ALOGPS logP 3.8 ALOGPS logP 3.9 ChemAxon logS -4.3 ALOGPS pKa (Strongest Acidic) 9.41 ChemAxon pKa (Strongest Basic) -6 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 37.3 Å2 ChemAxon Rotatable Bond Count 0 ChemAxon Refractivity 79.93 m3·mol-1 ChemAxon Polarizability 30.55 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9192 Caco-2 permeable + 0.875 P-glycoprotein substrate Substrate 0.6807 P-glycoprotein inhibitor I Non-inhibitor 0.8085 P-glycoprotein inhibitor II Non-inhibitor 0.8881 Renal organic cation transporter Non-inhibitor 0.6704 CYP450 2C9 substrate Non-substrate 0.7245 CYP450 2D6 substrate Non-substrate 0.9081 CYP450 3A4 substrate Substrate 0.7666 CYP450 1A2 substrate Inhibitor 0.9108 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Inhibitor 0.8209 CYP450 3A4 inhibitor Non-inhibitor 0.8156 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5528 Ames test Non AMES toxic 0.9109 Carcinogenicity Non-carcinogens 0.93 Biodegradation Not ready biodegradable 0.9319 Rat acute toxicity 1.8021 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7619 hERG inhibition (predictor II) Non-inhibitor 0.601
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Mass Spectrum (Electron Ionization) MS splash10-014i-3940000000-b80393e552aa78600070 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available 13C NMR Spectrum 1D NMR Not 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
- Humans
- 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
- 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]
- 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]
- 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
- Humans
- 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
- 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
- Humans
- 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