Hexestrol

Identification

Name
Hexestrol
Accession Number
DB07931  (DB08959)
Type
Small Molecule
Groups
Withdrawn
Description

A synthetic estrogen that has been used as a hormonal antineoplastic agent.

Structure
Thumb
Synonyms
  • 4,4'-(1,2-diethylethylene)diphenol
  • Erythrohexestrol
  • Hexanoestrol
  • Hexoestrolum
  • Meso-3,4-di(p-hydroxyphenyl)-n-hexane
  • Meso-hexestrol
  • Mesohexestrol
  • Synoestrolum
External IDs
NSC-9894
Product Ingredients
IngredientUNIICASInChI Key
Hexestrol diphosphate sodiumVK60X9E36E171399-06-7DNCWQZVLWAEATB-YHCLLLHXSA-J
International/Other Brands
Estrifar / Estronal / Hexoestrol (Tai Yu) / Synestrol (Biopharm) / Synoestrol
Categories
UNII
10BI795R7D
CAS number
84-16-2
Weight
Average: 270.3661
Monoisotopic: 270.161979948
Chemical Formula
C18H22O2
InChI Key
PBBGSZCBWVPOOL-HDICACEKSA-N
InChI
InChI=1S/C18H22O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h5-12,17-20H,3-4H2,1-2H3/t17-,18+
IUPAC Name
4-[(3R,4S)-4-(4-hydroxyphenyl)hexan-3-yl]phenol
SMILES
[H][C@](CC)(C1=CC=C(O)C=C1)[C@]([H])(CC)C1=CC=C(O)C=C1

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UAldo-keto reductase family 1 member C1Not AvailableHuman
UEstrogen receptor alphaNot AvailableHuman
UNuclear receptor subfamily 1 group I member 2Not AvailableHuman
UNuclear receptor subfamily 1 group I member 3Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinHexestrol may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinHexestrol may decrease the anticoagulant activities of (S)-Warfarin.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Hexestrol.
4-hydroxycoumarinHexestrol may decrease the anticoagulant activities of 4-hydroxycoumarin.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Hexestrol.
AbciximabHexestrol may decrease the anticoagulant activities of Abciximab.
AbituzumabHexestrol may increase the thrombogenic activities of Abituzumab.
AceclofenacAceclofenac may increase the thrombogenic activities of Hexestrol.
AcenocoumarolHexestrol may decrease the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidHexestrol may decrease the anticoagulant activities of Acetylsalicylic acid.
Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 2,357,985; U.S. Patent 2,421,401.

General References
  1. Liehr JG, Ballatore AM, Dague BB, Ulubelen AA: Carcinogenicity and metabolic activation of hexestrol. Chem Biol Interact. 1985 Oct;55(1-2):157-76. [PubMed:2998630]
External Links
PubChem Compound
192197
PubChem Substance
99444402
ChemSpider
166848
ChEMBL
CHEMBL9225
HET
HXS
Wikipedia
Hexestrol
PDB Entries
3cv6

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)185U.S. Patent 2,357,985; U.S. Patent 2,421,401.
Predicted Properties
PropertyValueSource
Water Solubility0.0139 mg/mLALOGPS
logP4.98ALOGPS
logP5.37ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.93ChemAxon
pKa (Strongest Basic)-5.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity82.66 m3·mol-1ChemAxon
Polarizability31.31 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9959
Blood Brain Barrier+0.7575
Caco-2 permeable+0.8705
P-glycoprotein substrateNon-substrate0.5375
P-glycoprotein inhibitor INon-inhibitor0.8556
P-glycoprotein inhibitor IINon-inhibitor0.8622
Renal organic cation transporterNon-inhibitor0.8652
CYP450 2C9 substrateNon-substrate0.7865
CYP450 2D6 substrateNon-substrate0.8813
CYP450 3A4 substrateNon-substrate0.602
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorNon-inhibitor0.7855
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.5469
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8156
Ames testNon AMES toxic0.9648
CarcinogenicityNon-carcinogens0.6254
BiodegradationNot ready biodegradable0.9528
Rat acute toxicity1.9859 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8238
hERG inhibition (predictor II)Non-inhibitor0.5976
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
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Stilbenes
Sub Class
Not Available
Direct Parent
Stilbenes
Alternative Parents
Phenylpropanes / 1-hydroxy-2-unsubstituted benzenoids / Organooxygen compounds / Hydrocarbon derivatives
Substituents
Stilbene / Phenylpropane / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Benzenoid / Monocyclic benzene moiety / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Aromatic homomonocyclic compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function
Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the in...
Gene Name
AKR1C1
Uniprot ID
Q04828
Uniprot Name
Aldo-keto reductase family 1 member C1
Molecular Weight
36788.02 Da
References
  1. 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. Maru BS, Tobias JH, Rivers C, Caunt CJ, Norman MR, McArdle CA: Potential use of an estrogen-glucocorticoid receptor chimera as a drug screen for tissue selective estrogenic activity. Bone. 2009 Jan;44(1):102-12. doi: 10.1016/j.bone.2008.09.016. Epub 2008 Oct 11. [PubMed:18976723]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [PubMed:20869355]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
Agonist at the canonical form of the receptor and at isoform 3 of the receptor.
General Function
Zinc ion binding
Specific Function
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital re...
Gene Name
NR1I3
Uniprot ID
Q14994
Uniprot Name
Nuclear receptor subfamily 1 group I member 3
Molecular Weight
39942.145 Da
References
  1. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [PubMed:20869355]

Drug created on September 15, 2010 15:27 / Updated on November 02, 2018 08:46