Raloxifene (CHEM016860)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesXML
Record Information
Version1.0
Creation Date2016-05-22 03:45:46 UTC
Update Date2016-11-09 01:15:29 UTC
Accession NumberCHEM016860
Identification
Common NameRaloxifene
ClassSmall Molecule
DescriptionRaloxifene is a second generation selective estrogen receptor modulator (SERM) that mediates anti-estrogenic effects on breast and uterine tissues, and estrogenic effects on bone, lipid metabolism, and blood coagulation. Exhibiting tissue-specific effects distinct from , raloxifene is the first of the benzothiophene group of antiestrogens to be labelled a SERM. Available in many countries worldwide, raloxifene was initially approved by the FDA in December, 1997 under the market name Evista® for the management and prevention of osteoporosis in postmenopausal women and reduction in risk for invasive breast cancer in postmenopausal women with osteoporosis or those who are at high risk for invasive breast cancer. However, it has a negligible effect on altering the development and progression of breast cancer itself. The most common causes of osteoporosis include postmenopausal deficiency of estrogen and age-related deterioration in bone homeostasis. Due to the risk of bone fractures that may lead to morbidities and reduced quality of life, the management of osteoporosis in postmenopausal women with the use of therapeutic agents in addition to concurrent therapies is critical. Due to the decline in estrogen levels in postmenopausal osteoporosis, hormone replacement therapy (HRT), such as estradiol, has been used to ameliorate the condition. However, due to the off-target actions by HRT, newer non-hormonal agents such as raloxifene and have been developed to reduce adverse events through selective pharmacological actions on tissue-specific therapeutic targets. The main effects of raloxifene are to preserve the bone mineral density and decrease the risk of breast cancer in postmenopausal women. Compared to estrogen and tamoxifen, raloxifene was not associated with an increased risk of uterine cancer and it does not cause endometrial proliferation. Although rare, there was an increased risk of venous thromboembolism during clinical trials of postmenopausal women receiving raloxifene. In addition, a clinical study consisting of postmenopausal women with documented coronary heart disease or at increased risk for coronary events showed an increased risk for fatal stroke with raloxifene therapy compared to placebo. It is strongly advised that the risk-benefit ratio is considered before starting raloxifene therapy in women at risk of thromboembolic disease or strokes, such as the prior history of stroke, transient ischemic attack, atrial fibrillation, hypertension, or cigarette smoking.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • ToxCast & Tox21 Chemicals
Contaminant TypeNot Available
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
(2-(4-Hydroxyphenyl)-6-hydroxybenzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)methanoneChEBI
KeoxifeneChEBI
LY 139481ChEBI
RaloxifenoChEBI
RaloxifenumChEBI
EvidenKegg
RaxetoKegg
LY-139481HMDB
RALHMDB
Raloxifene hydrochlorideHMDB
EvistaHMDB
Keoxifene hydrochlorideHMDB
Raloxifene HCLHMDB
Chemical FormulaC28H27NO4S
Average Molecular Mass473.583 g/mol
Monoisotopic Mass473.166 g/mol
CAS Registry Number84449-90-1
IUPAC Name2-(4-hydroxyphenyl)-3-{4-[2-(piperidin-1-yl)ethoxy]benzoyl}-1-benzothiophen-6-ol
Traditional Nameraloxifene
SMILESOC1=CC=C(C=C1)C1=C(C(=O)C2=CC=C(OCCN3CCCCC3)C=C2)C2=C(S1)C=C(O)C=C2
InChI IdentifierInChI=1S/C28H27NO4S/c30-21-8-4-20(5-9-21)28-26(24-13-10-22(31)18-25(24)34-28)27(32)19-6-11-23(12-7-19)33-17-16-29-14-2-1-3-15-29/h4-13,18,30-31H,1-3,14-17H2
InChI KeyGZUITABIAKMVPG-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl compounds
Direct ParentAryl-phenylketones
Alternative Parents
Substituents
  • Aryl-phenylketone
  • 3-aroylthiophene
  • Benzothiophene
  • 1-benzothiophene
  • Phenoxy compound
  • Benzoyl
  • Phenol ether
  • Thiophene carboxylic acid or derivatives
  • Alkyl aryl ether
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Monocyclic benzene moiety
  • Benzenoid
  • Piperidine
  • Heteroaromatic compound
  • Thiophene
  • Tertiary aliphatic amine
  • Tertiary amine
  • Organoheterocyclic compound
  • Azacycle
  • Ether
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic nitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginNot Available
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateNot Available
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00051 g/LALOGPS
logP5.45ALOGPS
logP5.69ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)8.89ChemAxon
pKa (Strongest Basic)7.95ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area70 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity135.48 m³·mol⁻¹ChemAxon
Polarizability52.55 ųChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-006t-9112200000-194dfc7c577ba3e76b98Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0udj-9010136000-3bb502413414534da20bSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0229-0035900000-dcf0b4afb1abd2691c7cSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0229-6600900000-ea14790ae9aed263379bSpectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-00di-0000900000-f184aabcb2eb146ebe92Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-00di-0000900000-3d3c761b7ff900186d5fSpectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-00di-0231900000-0fc53037915f41184d0bSpectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-00di-0000900000-6e89a56db5f01a157640Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0229-1800900000-cfc74f58ad18897ca1beSpectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-03di-8900000000-6cbb38555e813af5fa9cSpectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-00di-0000900000-76a62cda029e256d3f18Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-014j-0494000000-d01ec5346aa038f5719aSpectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-00di-0230900000-0fc53037915f41184d0bSpectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0229-0007900000-9eb122a555c8e7444904Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-014j-0494000000-6cde9fd49faae3fb307dSpectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-00di-0000900000-3015478097ea6bee8d7aSpectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-001i-9000000000-f3e7a5afa55ea1305028Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-0229-0007900000-2bda40c3103c3604b7c1Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-03di-0059000000-1bf6aa63d8858df8932fSpectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-03dr-0190000000-7ee2becffb54ed42c6e2Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-01p6-0092000000-86616f94829b2c365c93Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0114900000-e8c217b2f20574044c33Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03xs-4984400000-a2731ab247793dc0402eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014u-7296000000-82a010336a5451ab7f97Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-1012900000-c3bc16da6ed53c190cf7Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03kc-2149500000-8a3b4929414c1ff5dc90Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00l6-5596000000-26179eaf5995f4a2067bSpectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not Available
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB00481
HMDB IDHMDB0014624
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkRaloxifene
Chemspider ID4859
ChEBI ID8772
PubChem Compound ID5035
Kegg Compound IDC07228
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
1. Balfour JA, Goa KL: Raloxifene. Drugs Aging. 1998 Apr;12(4):335-41; discussion 342.
2. Khovidhunkit W, Shoback DM: Clinical effects of raloxifene hydrochloride in women. Ann Intern Med. 1999 Mar 2;130(5):431-9.
3. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, Norton L, Nickelsen T, Bjarnason NH, Morrow M, Lippman ME, Black D, Glusman JE, Costa A, Jordan VC: The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999 Jun 16;281(23):2189-97.
4. Bryant HU, Glasebrook AL, Yang NN, Sato M: An estrogen receptor basis for raloxifene action in bone. J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):37-44.
5. Clemett D, Spencer CM: Raloxifene: a review of its use in postmenopausal osteoporosis. Drugs. 2000 Aug;60(2):379-411.
6. Barrett-Connor E: Raloxifene: risks and benefits. Ann N Y Acad Sci. 2001 Dec;949:295-303.
7. Heringa M: Review on raloxifene: profile of a selective estrogen receptor modulator. Int J Clin Pharmacol Ther. 2003 Aug;41(8):331-45.
8. Authors unspecified: A STARring role for raloxifene? Lancet Oncol. 2006 Jun;7(6):443.
9. Diez-Perez A: Selective estrogen receptor modulators (SERMS). Arq Bras Endocrinol Metabol. 2006 Aug;50(4):720-34.
10. Silverman SL: New selective estrogen receptor modulators (SERMs) in development. Curr Osteoporos Rep. 2010 Sep;8(3):151-3. doi: 10.1007/s11914-010-0025-0.