Identification
NameRaloxifene
Accession NumberDB00481  (APRD00400)
TypeSmall Molecule
GroupsApproved, 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 KeyDetails
Raloxifene Hydrochloride4F86W47BR6 82640-04-8BKXVVCILCIUCLG-UHFFFAOYSA-NDetails
Product Images
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act RaloxifeneTablet60 mgOralActavis Pharma Company2012-06-19Not applicableCanada
EvistaTablet60 mg/1OralEli Lilly & Co. Ltd.1998-01-06Not applicableUs
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
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
OptrumaTablet, film coated60 mgOralEli Lilly Nederland B.V.1998-08-05Not applicableEu
PMS-raloxifeneTablet60 mgOralPharmascience Inc2011-09-19Not applicableCanada
RaloxifeneTablet60 mgOralPro Doc Limitee2013-11-28Not applicableCanada
Raloxifene HydrochlorideTablet60 mg/1OralKaiser Foundations Hospitals2014-05-29Not applicableUs
Raloxifene HydrochlorideTablet60 mg/1OralAvera Mc Kennan Hospital2015-03-01Not applicableUs
Raloxifene HydrochlorideTablet60 mg/1OralPrasco, Laboratories2014-03-012018-06-30Us
Teva-raloxifeneTablet60 mgOralTeva2009-07-28Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-raloxifeneTablet60 mgOralApotex Corporation2009-03-31Not applicableCanada
RaloxifeneTablet, film coated60 mg/1OralActavis Pharma Company2015-06-18Not applicableUs
RaloxifeneTablet, film coated60 mg/1OralAvera Mc Kennan Hospital2016-05-09Not applicableUs
Raloxifene HydrochlorideTablet60 mg/1OralCipla Limited2016-06-29Not applicableUs
Raloxifene HydrochlorideTablet60 mg/1OralAmerincan Health Packaging2014-11-132017-09-30Us
Raloxifene HydrochlorideTablet, film coated60 mg/1OralExelan Pharmaceuticals, Inc.2014-11-12Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralLucid Pharma Llc2015-08-28Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralAmneal Pharmaceuticals of New York Llc2016-01-20Not applicableUs
Raloxifene HydrochlorideTablet60 mg/1OralAmerincan Health Packaging2016-12-01Not 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 HydrochlorideTablet, film coated60 mg/1OralPrasco, Laboratories2015-08-28Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralAurobindo Pharma2015-08-28Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralSciegen Pharmaceuticals Inc.2016-10-12Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralAv Kare, Inc.2014-11-03Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralLiberty Pharmaceuticals, Inc.2014-11-12Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralKaiser Foundations Hospitals2016-07-08Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralAvera Mc Kennan Hospital2016-07-21Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralGlenmark Pharmaceuticals Inc.,Usa2016-03-22Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralDr. Reddy’s Laboratories Inc.2016-10-12Not applicableUs
Raloxifene TevaTablet, film coated60 mgOralTeva B.V.2010-04-29Not applicableEu
Raloxifene TevaTablet, film coated60 mgOralTeva B.V.2010-04-29Not applicableEu
Raloxifene TevaTablet, film coated60 mgOralTeva B.V.2010-04-29Not applicableEu
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
KeoxifeneNot Available
Brand mixturesNot Available
Categories
UNIIYX9162EO3I
CAS number84449-90-1
WeightAverage: 473.583
Monoisotopic: 473.166079047
Chemical FormulaC28H27NO4S
InChI KeyGZUITABIAKMVPG-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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Estrogen receptorProteinyes
agonist
HumanP03372 details
Estrogen receptor betaProteinyes
agonist
HumanQ92731 details
Serpin B9ProteinunknownNot AvailableHumanP50453 details
Trefoil factor 1ProteinunknownNot AvailableHumanP04155 details
Related Articles
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
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot 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
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
BexaroteneThe serum concentration of Raloxifene can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe metabolism of Raloxifene can be decreased when combined with Boceprevir.Approved, Investigational
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
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
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
DexamethasoneThe serum concentration of Raloxifene can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
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
EfavirenzThe serum concentration of Raloxifene can be decreased when it is combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Raloxifene can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Raloxifene can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Raloxifene can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtravirineThe serum concentration of Raloxifene can be decreased when it is combined with Etravirine.Approved
FluconazoleThe metabolism of Raloxifene can be decreased when combined with Fluconazole.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
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
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
ModafinilThe serum concentration of Raloxifene can be decreased when it is combined with Modafinil.Approved, Investigational
NafcillinThe serum concentration of Raloxifene can be decreased when it is combined with Nafcillin.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
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
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
PosaconazoleThe metabolism of Raloxifene can be decreased when combined with Posaconazole.Approved, Investigational, Vet 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
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
St. John's WortThe serum concentration of Raloxifene can be decreased when it is combined with St. John's Wort.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.Withdrawn
TelithromycinThe metabolism of Raloxifene can be decreased when combined with Telithromycin.Approved
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
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
ATC CodesG03XC01 — Raloxifene
AHFS Codes
  • 68:16.12
PDB EntriesNot Available
FDA labelDownload (2.11 MB)
MSDSDownload (57 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentAdenocarcinoma of the Prostate / Hormone-Resistant Prostate Cancer / Malignant Neoplasm of Prostate / 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
Tablet, film coatedOral60 mg/1
TabletOral60 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)
CA2101356 No1998-11-172013-07-27Canada
CA2158400 No2006-10-242015-09-15Canada
US5393763 No1995-07-282012-07-28Us
US6458811 No1997-03-102017-03-10Us
US6797719 No1997-03-102017-03-10Us
US6894064 No1997-03-102017-03-10Us
US8030330 No1997-03-102017-03-10Us
Properties
StateSolid
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
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0229-6600900000-ea14790ae9aed263379bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl compounds
Direct ParentAryl-phenylketones
Alternative Parents3-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
SubstituentsAryl-phenylketone / 3-aroylthiophene / Benzothiophene / 1-benzothiophene / Phenoxy compound / Benzoyl / Phenol ether / Thiophene carboxylic acid or derivatives / Alkyl aryl ether / 1-hydroxy-2-unsubstituted benzenoid
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors1-benzothiophenes, N-oxyethylpiperidine (CHEBI:45355 )

Targets

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 tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription fact...
Gene Name:
ESR1
Uniprot ID:
P03372
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 ]
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 manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by...
Gene Name:
ESR2
Uniprot ID:
Q92731
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
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
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
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 ]
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, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyz...
Gene Name:
AOX1
Uniprot ID:
Q06278
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
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 July 22, 2017 18:05