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

Structure

Similar Structures

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

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

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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Details1. Estradiol 17-beta-dehydrogenase 1

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]

Details2. Estrogen receptor alpha

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

Details1. Cytochrome P450 3A4

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 April 10, 2019 22:39

Equilin

Identification

Structure for Equilin (DB02187)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

Enzymes