Identification

Name
Raloxifene
Accession Number
DB00481  (APRD00400)
Type
Small Molecule
Groups
Approved, Investigational
Description

A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [PubChem]

Structure
Thumb
Synonyms
  • (2-(4-Hydroxyphenyl)-6-hydroxybenzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)methanone
  • Raloxifène
  • Raloxifeno
  • Raloxifenum
External IDs
J22.982B / LY 139481 / LY-139481
Product Ingredients
IngredientUNIICASInChI Key
Raloxifene Hydrochloride4F86W47BR682640-04-8BKXVVCILCIUCLG-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act RaloxifeneTablet60 mgOralActavis Pharma Company2012-06-19Not applicableCanada
EvistaTablet60 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2012-03-07Not applicableUs
EvistaTablet60 mg/1OralPd Rx Pharmaceuticals, Inc.1998-01-06Not applicableUs
EvistaTablet60 mg/1OralPhysicians Total Care, Inc.2000-05-11Not applicableUs00002 4165 02 nlmimage10 ef3af7c7
EvistaTablet60 mg/1OralEli Lilly & Co. Ltd.1998-01-06Not applicableUs
EvistaTablet60 mg/1OralEli Lilly & Co. Ltd.1998-01-06Not applicableUs
Evista (60mg)Tablet60 mgOralEli Lilly & Co. Ltd.1998-11-20Not applicableCanada
OptrumaTablet, film coated60 mgOralEli Lilly Nederland B.V.1998-08-05Not applicableEu
OptrumaTablet, film coated60 mgOralEli Lilly Nederland B.V.1998-08-05Not applicableEu
OptrumaTablet, film coated60 mgOralEli Lilly Nederland B.V.1998-08-05Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-raloxifeneTablet60 mgOralApotex Corporation2009-03-31Not applicableCanada
RaloxifeneTablet, film coated60 mg/1OralAvera Mc Kennan Hospital2016-05-09Not applicableUs
RaloxifeneTablet, film coated60 mg/1OralActavis Pharma Company2015-06-18Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralLiberty Pharmaceuticals, Inc.2014-11-12Not applicableUs
Raloxifene hydrochlorideTablet, film coated60 mg/1OralDr. Reddy’s Laboratories Inc.2016-10-12Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralAmneal Pharmaceuticals of New York Llc2016-01-20Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralTeva2014-03-28Not applicableUs00093 7290 56 nlmimage10 a73953ca
Raloxifene HydrochlorideTablet60 mg/1OralCamber Pharmaceuticals2014-09-24Not applicableUs31722 0256 30 nlmimage10 1b478ddc
Raloxifene HydrochlorideTablet, film coated60 mg/1OralKaiser Foundations Hospitals2016-10-12Not applicableUs
Raloxifene HydrochlorideTablet60 mg/1OralAmerincan Health Packaging2014-11-132017-09-30Us
International/Other Brands
Keoxifene
Categories
UNII
YX9162EO3I
CAS number
84449-90-1
Weight
Average: 473.583
Monoisotopic: 473.166079047
Chemical Formula
C28H27NO4S
InChI Key
GZUITABIAKMVPG-UHFFFAOYSA-N
InChI
InChI=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
IUPAC Name
2-(4-hydroxyphenyl)-3-{4-[2-(piperidin-1-yl)ethoxy]benzoyl}-1-benzothiophen-6-ol
SMILES
OC1=CC=C(C=C1)C1=C(C(=O)C2=CC=C(OCCN3CCCCC3)C=C2)C2=C(S1)C=C(O)C=C2

Pharmacology

Indication

For the prevention and treatment of osteoporosis in post-menopausal women, as well as prevention and treatment of corticosteroid-induced bone loss. Also for the reduction in the incidence of invasive breast cancer in postmenopausal women with osteoporosis or have a high risk for developing breast cancer.

Structured Indications
Pharmacodynamics

Raloxifene, a selective estrogen receptor modulator (SERM) of the benzothiophene class, is similar to tamoxifen in that it produces estrogen-like effects on bone and lipid metabolism, while antagonizing the effects of estrogen on breast and uterine tissue. Raloxifene differs chemically and pharmacologically from naturally occuring estrogens, synthetic steroidal and nonsteroidal compounds with estrogenic activity, and antiestrogens. Estrogens play an important role in the reproductive, skeletal, cardiovascular, and central nervous systems in women, and act principally by regulating gene expression. When estrogen binds to a ligand-binding domain of the estrogen receptor, biologic response is initiated as a result of a conformational change of the estrogen receptor, which leads to gene transcription through specific estrogen response elements of target gene promoters. The subsequent activation or repression of the target gene is mediated through 2 distinct transactivation domains of the receptor: AF-1 and AF-2. The estrogen receptor also mediates gene transcription using different response elements and other signalling pathways. The role of estrogen as a regulator of bone mass is well established. In postmenopausal women, the progressive loss of bone mass is related to decreased ovarian function and a reduction in the level of circulation estrogens. Estrogen also has favourable effects on blood cholesterol.

Mechanism of action

Raloxifene binds to estrogen receptors, resulting in differential expression of multiple estrogen-regulated genes in different tissues. Raloxifene produces estrogen-like effects on bone, reducing resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss. The maintenance of bone mass by raloxifene and estrogens is, in part, through the regulation of the gene-encoding transforming growth factor-β3 (TGF-β3), which is a bone matrix protein with antiosteoclastic properties. Raloxifene activates TGF-β3 through pathways that are estrogen receptor-mediated but involve DNA sequences distinct from the estrogen response element. The drug also binds to the estrogen receptor and acts as an estrogen agonist in preosteoclastic cells, which results in the inhibtion of their proliferative capacity. This inhibition is thought to contribute to the drug's effect on bone resorption. Other mechanisms include the suppression of activity of the bone-resorbing cytokine interleukin-6 promoter activity. Raloxifene also antagonizes the effects of estrogen on mammary tissue and blocks uterotrophic responses to estrogen. By competing with estrogens for the estrogen receptors in reproductive tissue, raloxifene prevents the transcriptional activation of genes containing the estrogen response element. As well, raloxifene inhibits the estradiol-dependent proliferation of MCF-7 human mammary tumor cells in vitro. The mechansim of action of raloxifene has not been fully determined, but evidence suggests that the drug's tissue-specific estrogen agonist or antagonist activity is related to the structural differences between the raloxifene-estrogen receptor complex (specifically the surface topography of AF-2) and the estrogen-estrogen receptor complex. Also, the existence of at least 2 estrogen receptors (ERα, ERβ) may contribute to the tissue specificity of raloxifene.

TargetActionsOrganism
AEstrogen receptor alpha
agonist
Human
AEstrogen receptor beta
agonist
Human
USerpin B9Not AvailableHuman
UTrefoil factor 1Not AvailableHuman
Absorption

Approximately 60% of an oral dose is absorbed, but presystemic glucuronide conjugation is extensive. Absolute bioavailability of raloxifene is 2.0%

Volume of distribution
  • 2348 L/kg [oral administration of single doses ranging from 30 to 150 mg]
Protein binding

95%

Metabolism

Hepatic, raloxifene undergoes extensive first-pass metabolism to the glucuronide conjugates: raloxifene-4'-glucuronide, raloxifene-6-glucuronide, and raloxifene-6, 4'-diglucuronide. No other metabolites have been detected, providing strong evidence that raloxifene is not metabolized by cytochrome P450 pathways

Route of elimination

Raloxifene is primarily excreted in feces, and less than 0.2% is excreted unchanged in urine.

Half life

27.7

Clearance
  • 44.1 L/kg•hr [Healthy Postmenopausal Woman with Single Dose]
  • 47.4 L/kg•hr [Healthy Postmenopausal Woman with Multiple Dose]
  • Oral cl=44.1 L/kg•hr
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AmiodaroneThe metabolism of Raloxifene can be decreased when combined with Amiodarone.Approved, Investigational
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Raloxifene.Approved, Investigational
AprepitantThe serum concentration of Raloxifene can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Raloxifene can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Raloxifene can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Raloxifene is combined with Atorvastatin.Approved
BoceprevirThe metabolism of Raloxifene can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Raloxifene can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Raloxifene can be decreased when it is combined with Bosentan.Approved, Investigational
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Raloxifene.Approved, Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Raloxifene.Approved
CarbamazepineThe metabolism of Raloxifene can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Raloxifene can be increased when it is combined with Ceritinib.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Raloxifene.Withdrawn
CholestyramineCholestyramine can cause a decrease in the absorption of Raloxifene resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
ClarithromycinThe metabolism of Raloxifene can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Raloxifene can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Raloxifene can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Raloxifene can be decreased when combined with Cobicistat.Approved
ColesevelamColesevelam can cause a decrease in the absorption of Raloxifene resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
ColestipolColestipol can cause a decrease in the absorption of Raloxifene resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
ConivaptanThe serum concentration of Raloxifene can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Raloxifene can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Raloxifene can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Raloxifene can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Raloxifene can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Raloxifene can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Raloxifene can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Raloxifene can be decreased when combined with Delavirdine.Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Raloxifene.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Raloxifene.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Raloxifene.Experimental
DihydroergotamineThe metabolism of Raloxifene can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Raloxifene can be decreased when combined with Diltiazem.Approved
DoxycyclineThe metabolism of Raloxifene can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Raloxifene can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of Raloxifene can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Raloxifene.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Raloxifene.Approved
ErythromycinThe metabolism of Raloxifene can be decreased when combined with Erythromycin.Approved, Vet Approved
FluconazoleThe metabolism of Raloxifene can be decreased when combined with Fluconazole.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Raloxifene.Approved
FluvoxamineThe metabolism of Raloxifene can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Raloxifene can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Raloxifene can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Raloxifene can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Raloxifene can be increased when it is combined with Fusidic Acid.Approved
IdelalisibThe serum concentration of Raloxifene can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Raloxifene can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Raloxifene can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Raloxifene can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Raloxifene can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Raloxifene can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Raloxifene can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Raloxifene can be decreased when combined with Ketoconazole.Approved, Investigational
LevothyroxineRaloxifene can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Raloxifene.Approved, Investigational
LopinavirThe metabolism of Raloxifene can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Raloxifene can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Raloxifene can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Raloxifene can be increased when combined with Lumacaftor.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Raloxifene.Illicit, Investigational, Withdrawn
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Raloxifene.Experimental
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Raloxifene.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Raloxifene.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Raloxifene.Experimental
MifepristoneThe serum concentration of Raloxifene can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Raloxifene can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Raloxifene can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Raloxifene can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Raloxifene can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Raloxifene can be increased when combined with Nevirapine.Approved
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Raloxifene.Approved, Investigational
NilotinibThe metabolism of Raloxifene can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Raloxifene can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Raloxifene can be increased when it is combined with Osimertinib.Approved
OspemifeneThe risk or severity of adverse effects can be increased when Raloxifene is combined with Ospemifene.Approved
PalbociclibThe serum concentration of Raloxifene can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Raloxifene can be increased when combined with Pentobarbital.Approved, Vet Approved
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Raloxifene.Approved, Investigational, Vet Approved, Withdrawn
PhenobarbitalThe metabolism of Raloxifene can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Raloxifene can be increased when combined with Phenytoin.Approved, Vet Approved
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Raloxifene.Approved
PosaconazoleThe metabolism of Raloxifene can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Raloxifene.Approved
PrimidoneThe metabolism of Raloxifene can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of Raloxifene can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Raloxifene can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Raloxifene can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Raloxifene can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Raloxifene can be decreased when combined with Ritonavir.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Raloxifene.Approved
SaquinavirThe metabolism of Raloxifene can be decreased when combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Raloxifene can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Raloxifene can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Raloxifene can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Raloxifene.Approved
St. John's WortThe serum concentration of Raloxifene can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Raloxifene can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Raloxifene can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Raloxifene can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Raloxifene can be decreased when combined with Telithromycin.Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Raloxifene.Experimental
TiclopidineThe metabolism of Raloxifene can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Raloxifene can be decreased when it is combined with Tocilizumab.Approved
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Raloxifene.Approved, Experimental
VenlafaxineThe metabolism of Raloxifene can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Raloxifene can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Raloxifene can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Raloxifene can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

References

Synthesis Reference

Massimo Ferrari, Fabrizio Zinetti, Paolo Belotti, "Process for preparing raloxifene hydrochloride." U.S. Patent US20070100147, issued May 03, 2007.

US20070100147
General References
  1. Authors unspecified: A STARring role for raloxifene? Lancet Oncol. 2006 Jun;7(6):443. [PubMed:16750489]
  2. Heringa M: Review on raloxifene: profile of a selective estrogen receptor modulator. Int J Clin Pharmacol Ther. 2003 Aug;41(8):331-45. [PubMed:12940590]
  3. Barrett-Connor E: Raloxifene: risks and benefits. Ann N Y Acad Sci. 2001 Dec;949:295-303. [PubMed:11795366]
  4. Khovidhunkit W, Shoback DM: Clinical effects of raloxifene hydrochloride in women. Ann Intern Med. 1999 Mar 2;130(5):431-9. [PubMed:10068418]
  5. 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. [PubMed:10376571]
  6. 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. [PubMed:10418979]
  7. Balfour JA, Goa KL: Raloxifene. Drugs Aging. 1998 Apr;12(4):335-41; discussion 342. [PubMed:9571395]
  8. Clemett D, Spencer CM: Raloxifene: a review of its use in postmenopausal osteoporosis. Drugs. 2000 Aug;60(2):379-411. [PubMed:10983739]
  9. 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. [PubMed:20603714]
  10. Diez-Perez A: Selective estrogen receptor modulators (SERMS). Arq Bras Endocrinol Metabol. 2006 Aug;50(4):720-34. [PubMed:17117297]
External Links
Human Metabolome Database
HMDB14624
KEGG Compound
C07228
PubChem Compound
5035
PubChem Substance
46506514
ChemSpider
4859
BindingDB
19441
ChEBI
8772
ChEMBL
CHEMBL81
Therapeutic Targets Database
DAP000792
PharmGKB
PA451221
IUPHAR
2820
Guide to Pharmacology
GtP Drug Page
HET
RAL
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Raloxifene
ATC Codes
G03XC01 — Raloxifene
AHFS Codes
  • 68:16.12 — Estrogen Agonist-antagonists
PDB Entries
1err / 1qkn / 2jfa / 2qxs / 2y05
FDA label
Download (2.11 MB)
MSDS
Download (57 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentAdenocarcinoma of the Prostate / Hormone-Resistant Prostate Cancer / Prostate Cancer / Stage IV Prostate Cancer1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
1Not Yet RecruitingTreatmentHealthy Volunteers1
2CompletedPreventionCancer, Breast1
2CompletedPreventionEndometrial Safety / Vasomotor Symptoms1
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentEndometrial Cancers1
2CompletedTreatmentEndometriosis / Pelvic Pain1
2CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
2CompletedTreatmentUrinary Bladder Neoplasms1
2CompletedTreatmentOne to five years postmenopausal1
2RecruitingTreatmentStage I Prostate Adenocarcinoma / Stage II Prostate Adenocarcinoma1
2, 3CompletedTreatmentAlzheimer's Disease (AD)1
3CompletedPreventionAging / Cognition1
3CompletedPreventionCancer, Breast1
3CompletedPreventionCardiovascular Disease (CVD) / Neoplasms, Breast1
3CompletedPreventionOsteopenia1
3CompletedPreventionBone destruction1
3CompletedTreatmentBone destruction / Endometrial Hyperplasia1
3CompletedTreatmentNegative Symptoms of Schizophrenia in Post-menopausal Women1
3CompletedTreatmentPolycystic Ovaries Syndrome1
3CompletedTreatmentPostmenopausal Osteoporosis (PMO)3
3RecruitingTreatmentPsychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
3TerminatedNot AvailableOne to five years postmenopausal1
3Unknown StatusTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
4CompletedPreventionHealthy Volunteers1
4CompletedTreatmentCompliance / Postmenopausal Osteoporosis (PMO)1
4CompletedTreatmentDepressive State / Perimenopausal Depression1
4CompletedTreatmentOsteoporosis, Post-Menopausal2
4CompletedTreatmentPostmenopausal Osteoporosis (PMO)3
4CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
4CompletedTreatmentSchizophrenic Disorders1
4CompletedTreatmentBone destruction4
4Not Yet RecruitingTreatmentDepressive Syndrome1
4RecruitingTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
4RecruitingTreatmentSchizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
4TerminatedPreventionPostmenopausal Osteoporosis (PMO)1
Not AvailableActive Not RecruitingNot AvailablePostmenopausal Osteoporosis (PMO)1
Not AvailableCompletedNot AvailableAdenocarcinomas / Esophageal Cancers / Squamous Cell Carcinoma (SCC)1
Not AvailableCompletedNot AvailableBone destruction1
Not AvailableCompletedPreventionCancer, Breast1
Not AvailableCompletedSupportive CareBone destruction / Cancer, Breast / Menopausal Symptoms1
Not AvailableNot Yet RecruitingTreatmentRheumatoid Arthritis1
Not AvailableRecruitingNot AvailableSelective Estrogen Receptor Modulator (SERM)1
Not AvailableTerminatedTreatmentPolycystic Ovarian Syndrome1
Not AvailableUnknown StatusPreventionCancer, Breast1

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
Dosage forms
FormRouteStrength
TabletOral60 mg
Tablet, film coatedOral60 mg
TabletOral60 mg/1
Tablet, film coatedOral60 mg/1
Prices
Unit descriptionCostUnit
Evista 60 mg tablet4.37USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5393763No1995-07-282012-07-28Us
CA2158400No2006-10-242015-09-15Canada
CA2101356No1998-11-172013-07-27Canada
US6458811No1997-03-102017-03-10Us
US6894064No1997-03-102017-03-10Us
US6797719No1997-03-102017-03-10Us
US8030330No1997-03-102017-03-10Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)143-147 °CNot Available
water solubility0.25mg/LNot Available
logP5.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000512 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity135.48 m3·mol-1ChemAxon
Polarizability52.55 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9865
Blood Brain Barrier+0.8661
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.7751
P-glycoprotein inhibitor INon-inhibitor0.6231
P-glycoprotein inhibitor IIInhibitor0.9366
Renal organic cation transporterInhibitor0.634
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5198
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorInhibitor0.8986
CYP450 3A4 inhibitorInhibitor0.7617
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8222
Ames testNon AMES toxic0.8487
CarcinogenicityNon-carcinogens0.9433
BiodegradationNot ready biodegradable0.9587
Rat acute toxicity2.5287 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6322
hERG inhibition (predictor II)Inhibitor0.5779
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
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0229-0035900000-dcf0b4afb1abd2691c7c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0229-6600900000-ea14790ae9aed263379b

Taxonomy

Description
This compound 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.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
3-aroylthiophenes / 1-benzothiophenes / Thiophene carboxylic acids and derivatives / Phenoxy compounds / Phenol ethers / Benzoyl derivatives / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Heteroaromatic compounds
show 5 more
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
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
1-benzothiophenes, N-oxyethylpiperidine (CHEBI:45355)

Targets

Details
1. Estrogen receptor alpha
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Khovidhunkit W, Shoback DM: Clinical effects of raloxifene hydrochloride in women. Ann Intern Med. 1999 Mar 2;130(5):431-9. [PubMed:10068418]
  2. 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. [PubMed:10376571]
  3. 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. [PubMed:10418979]
  4. Figtree GA, Lu Y, Webb CM, Collins P: Raloxifene acutely relaxes rabbit coronary arteries in vitro by an estrogen receptor-dependent and nitric oxide-dependent mechanism. Circulation. 1999 Sep 7;100(10):1095-101. [PubMed:10477535]
  5. Schafer JI, Liu H, Tonetti DA, Jordan VC: The interaction of raloxifene and the active metabolite of the antiestrogen EM-800 (SC 5705) with the human estrogen receptor. Cancer Res. 1999 Sep 1;59(17):4308-13. [PubMed:10485477]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Scott JA, Da Camara CC, Early JE: Raloxifene: a selective estrogen receptor modulator. Am Fam Physician. 1999 Sep 15;60(4):1131-9. [PubMed:10507743]
  8. Matsumoto T: [Selective estrogen receptor modulators (SERMs)]. Clin Calcium. 2006 Sep;16(9):1520-25. [PubMed:16951478]
  9. Moen MD, Keating GM: Raloxifene: a review of its use in the prevention of invasive breast cancer. Drugs. 2008;68(14):2059-83. [PubMed:18778124]
Details
2. Estrogen receptor beta
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. 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. [PubMed:10418979]
  2. Iannone MA, Consler TG, Pearce KH, Stimmel JB, Parks DJ, Gray JG: Multiplexed molecular interactions of nuclear receptors using fluorescent microspheres. Cytometry. 2001 Aug 1;44(4):326-37. [PubMed:11500849]
  3. Zhou W, Koldzic-Zivanovic N, Clarke CH, de Beun R, Wassermann K, Bury PS, Cunningham KA, Thomas ML: Selective estrogen receptor modulator effects in the rat brain. Neuroendocrinology. 2002 Jan;75(1):24-33. [PubMed:11810032]
  4. Sun J, Huang YR, Harrington WR, Sheng S, Katzenellenbogen JA, Katzenellenbogen BS: Antagonists selective for estrogen receptor alpha. Endocrinology. 2002 Mar;143(3):941-7. [PubMed:11861516]
  5. Kim IY, Seong DH, Kim BC, Lee DK, Remaley AT, Leach F, Morton RA, Kim SJ: Raloxifene, a selective estrogen receptor modulator, induces apoptosis in androgen-responsive human prostate cancer cell line LNCaP through an androgen-independent pathway. Cancer Res. 2002 Jul 1;62(13):3649-53. [PubMed:12097269]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Granzyme B inhibitor.
Specific Function
Cysteine-type endopeptidase inhibitor activity involved in apoptotic process
Gene Name
SERPINB9
Uniprot ID
P50453
Uniprot Name
Serpin B9
Molecular Weight
42403.185 Da
References
  1. Krieg AJ, Krieg SA, Ahn BS, Shapiro DJ: Interplay between estrogen response element sequence and ligands controls in vivo binding of estrogen receptor to regulated genes. J Biol Chem. 2004 Feb 6;279(6):5025-34. Epub 2003 Nov 14. [PubMed:14617632]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. May inhibit the growth of calcium oxalate crystals in urine.
Specific Function
Growth factor activity
Gene Name
TFF1
Uniprot ID
P04155
Uniprot Name
Trefoil factor 1
Molecular Weight
9149.435 Da
References
  1. Krieg AJ, Krieg SA, Ahn BS, Shapiro DJ: Interplay between estrogen response element sequence and ligands controls in vivo binding of estrogen receptor to regulated genes. J Biol Chem. 2004 Feb 6;279(6):5025-34. Epub 2003 Nov 14. [PubMed:14617632]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [PubMed:17101742]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Details
3. Aldehyde oxidase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xanthine dehydrogenase activity
Specific Function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name
AOX1
Uniprot ID
Q06278
Uniprot Name
Aldehyde oxidase
Molecular Weight
147916.735 Da
References
  1. Obach RS: Potent inhibition of human liver aldehyde oxidase by raloxifene. Drug Metab Dispos. 2004 Jan;32(1):89-97. [PubMed:14709625]
  2. Obach RS, Huynh P, Allen MC, Beedham C: Human liver aldehyde oxidase: inhibition by 239 drugs. J Clin Pharmacol. 2004 Jan;44(1):7-19. [PubMed:14681337]
  3. Sahi J, Khan KK, Black CB: Aldehyde oxidase activity and inhibition in hepatocytes and cytosolic fractions from mouse, rat, monkey and human. Drug Metab Lett. 2008 Aug;2(3):176-83. [PubMed:19356090]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Details
5. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 13, 2017 21:49