Identification

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

Raloxifene 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.6,12 Exhibiting tissue-specific effects distinct from estradiol, raloxifene is the first of the benzothiophene group of antiestrogens to be labelled a SERM.7 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.Label 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 tamoxifen have been developed to reduce adverse events through selective pharmacological actions on tissue-specific therapeutic targets.12

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.1 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.Label 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.Label

Structure
Thumb
Synonyms
  • (2-(4-Hydroxyphenyl)-6-hydroxybenzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)methanone
  • Raloxifène
  • Raloxifene
  • 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 RaloxifeneTabletOralTEVA Canada Limited2012-06-19Not applicableCanada
EvistaTablet60 mg/1OralEli Lilly and Company1998-01-06Not applicableUs
EvistaTablet60 mg/1OralEli Lilly and Company2006-04-172006-04-17Us0002 416520180810 16125 1ebbynl
EvistaTablet60 mg/1OralPd Rx Pharmaceuticals, Inc.1998-01-062018-07-17Us
EvistaTablet60 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2012-03-072014-12-31Us
EvistaTablet60 mg/1OralPhysicians Total Care, Inc.2000-05-11Not applicableUs00002 4165 02 nlmimage10 ef3af7c7
Evista (60mg)TabletOralEli 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
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-raloxifeneTabletOralApotex Corporation2009-03-31Not applicableCanada
PMS-raloxifeneTabletOralPharmascience Inc2011-09-192020-04-22Canada
RaloxifeneTablet, film coated60 mg/1OralAvera McKennan Hospital2016-05-092017-05-24Us
RaloxifeneTablet, film coated60 mg/1OralActavis Pharma Company2015-06-18Not applicableUs0591 236720180907 15195 xsrogv
Raloxifene HydrochlorideTablet60 mg/1Oralbryant ranch prepack2016-06-29Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralTeva Pharmaceuticals USA, Inc.2014-03-28Not applicableUs00093 7290 56 nlmimage10 a73953ca
Raloxifene HydrochlorideTablet60 mg/1OralCamber Pharmaceuticals2014-09-24Not applicableUs31722 0256 30 nlmimage10 1b478ddc
Raloxifene hydrochlorideTablet, film coated60 mg/1OralAphena Pharma Solutions Tennessee, Inc.2016-10-12Not applicableUs
Raloxifene hydrochlorideTablet, film coated60 mg/1OralDr.Reddy’s Laboratories Inc2016-10-12Not applicableUs
Raloxifene HydrochlorideTablet, film coated60 mg/1OralAphena Pharma Solutions Tennessee, Inc.2015-08-28Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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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

Indicated for the prevention and treatment of osteoporosis in postmenopausal women, as well as prevention and treatment of corticosteroid-induced bone loss.Label

Indicated for the reduction in the risk of invasive breast cancer in postmenopausal women with osteoporosis or postmenopausal women with a high risk for invasive breast cancer.Label

Associated Conditions
Pharmacodynamics

Raloxifene belongs to the selective estrogen receptor modulator (SERM) drug class that exhibits estrogenic effects on bone and lipid metabolism while mediating anti-estrogenic effects on uterine endometrium and breast tissues.7 On skeletal tissues, raloxifene stimulates bone-depositing osteoblasts and inhibits bone-resorbing osteoclasts12 to augument bone mineral density.7 Raloxifene produces estrogen-like effects on bone, reducing the resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss.Label In three randomized, placebo-controlled trials in Europe, postmenopausal women receiving raloxifene at variable doses of 30 to 150 mg daily demonstrated significant increases in bone mineral density in the lumbar spine, total hip, femoral neck and total body compared to placebo.7 In the MORE and RUTH trials, there were fewer incidences of vertebral fractures in postmeopausal women receiving raloxifene compared to placebo.6 In a eight-week study evaluating short-term effects of raloxifene in healthy postmenopausal women, there was a decrease in the bone turnover markers, such as serum alkaline phosphatase level, serum osteocalcin level and urinary calcium excretion.7

Raloxifene was shown to inhibit estrogen-dependent proliferation of human breast cancer cells in vitro and development of induced mammary tumors in rats in vivo.4 In adult female rats, raloxifene produced a greater regression of the mammary gland than tamoxifen.4 The MORE trial was a multicenter, randomized, double-blind clinical trial that investigated the long-term effects of the drug therapy in European and American postmenopausal women receiving raloxifene for 40 months.2 Additionally, a reduction in the incidence of invasive breast cancer was also demonstrates in the CORE and RUTH trials.6 Study findings demonstrated that compared to placebo, the risk of invasive breast cancer was decreased by 76% among postmenopausal women with osteoporosis. There was a decrease in the risk of estrogen receptor-positive breast cancer by 90% but there was no increase in the risk of endometrial cancer. Unlike hormone replacement therapy, raloxifene does not mediate proliferative or stimulatory effects on endometrial tissue. Findings from both animal and human studies demonstrated no significant changes in the histologic appearance of the endometrium.7

Raloxifene promotes estrogen-like effects on lipid metabolism. In a European trial that evaluated lipid profiles following raloxifene therapy over the 24-month period, there were significant decreases in the serum concentrations of total and low-density lipoprotein (LDL) cholesterol over a 24-month period of raloxifene therapy.7 Raloxifene is not associated with causing alterations in the serum levels of HDL cholesterol or triglycerides.7 As the HDL choesterol level is considered a strong inverse predictor of cardiovascular disease in women, the cardioprotective effects of raloxifene were questioned. Due to limited data on the long-term trials, it is not possible to determine whether the small lipid effects produced by raloxifene correlate with a smaller degree of cardioprotective activity compared with hormone replacement therapy.7

Mechanism of action

Raloxifene is a selective estrogen receptor modulator that acts as both an estrogen agonist and antagonist via differential effects on the tissue-specific estrogen receptors. Based on the findings of competitive binding assays, raloxifene displays binding affinity that is similar to that of estradiol4, the predominant circulating estrogen.9 Estrogens play variable roles at different tissues in females, including the bone, breasts, uterus and liver, by binding to the steroid nuclear hormone receptors, Estrogen Receptor alpha (ERα) or Estrogen Receptor beta (ERβ).9 These receptors are normally bound to the Heat Shock Protein 90 (Hsp90) when unbound to the ligand. Ligand binding induces a conformational change in the receptor that promotes dissociation of the receptor from Hsp90, dimerization and translocation into the nucleus. This movement into the nucleus allows the receptor to bind to genomic locations based on sequence recognition of the DNA binding domain, also known as the Estrogen Response Elements (EREs).9

In bones, endogenous estrogens normally modulate multiple DNA response elements, including the gene-encoding transforming growth factor-β3 (TGF-β3), which is a cytokine embedded in the bone matrix.12 TGF-β3 plays an important role in bone remodelling8 by working with other cytokines to induce production of osteoblasts, such as IL-63, and attenuate the activity of osetoclasts. Estrogens typically maintain the bone integrity by inhibiting the cytokines that recruit osteoclasts and oppose the bone-resorbing, Ca2+-mobilizing action of parathyroid hormone. In contrast, estrogens promote osteoblast proliferation, augment the production of TGF-β3 and bone morphogenic proteins, and inhibit apoptosis.12 Mimicking the action of endogenous estrogen in bone tissues, raloxifene binds to the estrogen receptor to influence gene transcription through interactions with the estrogen response element (ERE) and a distinct DNA target, the raloxifene response element (RRE).5 It occupies the same ER ligand binding site as estrogen.11 Upon binding, raloxifene induces a conformational change of the receptor, allowing mediation of direct binding to transcriptional elements by accessory proteins. Increased expression of bone matrix proteins, such as alkaline phosphatase, osteonectin, osteocalcin and collagen may be seen.5 The agonistic or antagonistic action of raloxifene depends on the extent of recruitment of coactivators and corepressors to estrogen receptor (ER) target gene promotors.Label In breast tissues, raloxifene acts as an estrogen receptor antagonist to attenuate the estrogen-dependent proliferative effects of epithelial cell expansion. In addition to the antiproliferative effects, raloxifene prevents the production of cytokines and recruitment of macrophages and lymphocytes into tumor mass.10

TargetActionsOrganism
AEstrogen receptor alpha
agonist
Humans
AEstrogen receptor beta
agonist
Humans
USerpin B9Not AvailableHumans
UTrefoil factor 1Not AvailableHumans
Additional Data Available
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Absorption

Raloxifene is well absorbed from the gastrointestinal tract, with approximately 60% fo the drug being absorbed following oral administration.12 Due to the extensive first-pass hepatic metabolism that involves glucuronide conjugation, the absolute oral bioavailability of raloxifene is about 2%.12 Following oral ingestion of a single dose or multiple dose of raloxifen in healthy postmenopausal women, the mean peak plasma concentrations (Cmax) were 0.50 and 1.36 ng/mL, respectively, and the AUC values were 27.2 and 24.2 ngxhr/mL, respectively. The time to reach Cmax following a single or multiple oral doses were 27.7 and 32.5 hours, respectively.Label Although not clinically significant, oral ingestion of raloxifene with high-fat meals is thought to increase the systemic bioavailability of the drug7 by increasnig the peak plasma concentrations (Cmax) and AUC by 28% and 16%, respectively.Label

Volume of distribution

Following oral administration of single doses randing from 30 to 150 mg in postmenopausal women, the volume of distribution was about 2348 L/kg. Following oral administration of multiple doses, the value increased to 2853 L/kg. Raloxifene is widely distributed in the tissues. It is not known whether raloxifene is excreted in human milk.Label

Protein binding

About 95% of raloxifene and its glucuronide metabolites are bound to plasma proteins.Label Although this is a relatively high protein binding profile, in vitro studies suggest that raloxifene and its metabolites do not significantly interact with binding of highly protein-bound drugs.7 FDA Label still advises patients to use raloxifene with caution co-administering with other highly protein-bound drugs.Label

Metabolism

Raloxifene is reported to undergo metabolism in the intestines and liver devoid of cytochrome P450 pathway.7 It is extensively metabolized, where less than 1% of the total dose exists as unchanged compound.Label It mainly undergoes first-pass metabolism to form glucuronide conjugates, raloxifene-4'-glucuronide (raloxifene-4'-β-glucuronide), raloxifene-6-glucuronide (raloxifene-6-β-glucuronide), and raloxifene-6,4'-diglucuronide. No other metabolites have been detected in human plasma. The terminal log-linear portions of the plasma concentration curves for raloxifene and the glucuronides are generally parallel. This is consistent with interconversion of raloxifene and the glucuronide metabolites.Label

Route of elimination

Raloxifene predominantly undergoes fecal excretion, with less than 0.2% of the dose being excreted in the urine as unchanged form of the compound and less than 6% of the dose being excreted as glucuronide conjugates. Co-administration with cholestyramine, a bile acid sequestrant, was shown to reduce the enterohepatic recycling of raloxifene by 60%.12

Half life

The average plasma elimination half-life of raloxifene ranges from 27 to 32 hours.7,12 The prolonged half-life has been attributed to the drug's reversible systemic metabolism and significant enterohepatic cycling.7

Clearance

Following intravenous administration, raloxifene was shown to be cleared at a rate approximating hepatic blood flow. The apparent oral clearance is reported to be 44.1 L/kgxhr. The clearance can range from 40 to 60L/kgxhr following chronic dosing. In healthy postmenopausal women receiving multiple oral dose, the mean clearance was 47.4 L/kgxhr. Apparent clearance can be reduced by 56% in patients with hepatic impairment.Label

Toxicity

LD50 and Overdose

The oral LD50 value in rats is > 5000 mg/kg, which is about 810 times the human dose.MSDS In monkeys, no mortality was seen after a single oral dose of 1000 mg/kg.Label No cases of raloxifene overdose have been reported during clinical trials. A rare postmarketing report of a non-fatal overdose after oral ingestion of 1.5 g has been reported. Common adverse events of leg cramps, hot flushes, and dizziness have been reported with the use of raloxifene at doses of greater than 180 mg. More serious adverse event of venous thromboembolic events were observed with raloxifene.4 Two 18-month-old children accidentally ingested 180 mg of raloxifene and symptoms of ataxia, dizziness, vomiting, rash, diarrhea, tremor, flushing, and elevated alkaline phosphatase levels were reported. There is no known antidote for raloxifene. Label

Nonclinical Toxicology

In a two-year mouse carcinogenicity study at raloxifene doses that are higher than the human therapeutic doses, there was an increased incidence of benign and malignant ovarian tumors of granulosa or theca cell origin. Another study showed an increased incidence of testicular interstitial cell tumors, prostatic adenomas, adenocarcinomas, and prostatic leiomyoblastoma in male mice receiving doses higher than human therapeutic doses. There was no evidence of the genotoxic potential of raloxifene in bacterial mutagenicity assays, in vitro rat DNA assays, or other in vitro rodent cell line assays. When assessing effects on the reproductive system of male and female rats, raloxifene caused lack of pregnancy and disruptions in estrous cycles and inhibited ovulation at dose of 0.1 to 10 mg/kg/day. Administration of raloxifene during the preimplantation period at doses greater than 0.1 mg/kg resulted in delayed and disrupted embryo implantation, further leading to prolonged gestation and reduced litter size. There were no effects on sperm production or quality or reproductive performance in male rats. The effects on the fertility by raloxifene were reversible.Label

Use in special populations

The use of raloxifene in pregnant or nursing women is not advised. Although there are no specific dosing adjustment guidelines, caution should be undertaken when administering raloxifene in geriatric patients or patients with renal or hepatic impairment.Label

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Raloxifene.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Raloxifene.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Raloxifene.
AbemaciclibAbemaciclib may decrease the excretion rate of Raloxifene which could result in a higher serum level.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Raloxifene.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Raloxifene.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Raloxifene.
AcetylcysteineThe excretion of Raloxifene can be decreased when combined with Acetylcysteine.
AdenineThe metabolism of Raloxifene can be decreased when combined with Adenine.
AfatinibAfatinib may decrease the excretion rate of Raloxifene which could result in a higher serum level.
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Food Interactions
  • Avoid excessive or chronic alcohol consumption. Excessive and chronic alcohol consumption may be associated with vitamin D deficiency.
  • Take with or without food. The absorption is unaffected by food.

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. 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]
  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. Balfour JA, Goa KL: Raloxifene. Drugs Aging. 1998 Apr;12(4):335-41; discussion 342. [PubMed:9571395]
  5. Clemett D, Spencer CM: Raloxifene: a review of its use in postmenopausal osteoporosis. Drugs. 2000 Aug;60(2):379-411. [PubMed:10983739]
  6. 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]
  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. Yang NN, Venugopalan M, Hardikar S, Glasebrook A: Identification of an estrogen response element activated by metabolites of 17beta-estradiol and raloxifene. Science. 1996 Aug 30;273(5279):1222-5. [PubMed:8703055]
  9. Palmisano BT, Zhu L, Stafford JM: Role of Estrogens in the Regulation of Liver Lipid Metabolism. Adv Exp Med Biol. 2017;1043:227-256. doi: 10.1007/978-3-319-70178-3_12. [PubMed:29224098]
  10. Yaghjyan L, Colditz GA: Estrogens in the breast tissue: a systematic review. Cancer Causes Control. 2011 Apr;22(4):529-40. doi: 10.1007/s10552-011-9729-4. Epub 2011 Feb 1. [PubMed:21286801]
  11. Diez-Perez A: Selective estrogen receptor modulators (SERMS). Arq Bras Endocrinol Metabol. 2006 Aug;50(4):720-34. [PubMed:17117297]
  12. 35. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 438-439). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  13. EVISTA (raloxifene hydrochloride) Tablet for Oral Use - FDA Label [Link]
External Links
Human Metabolome Database
HMDB0014624
KEGG Compound
C07228
PubChem Compound
5035
PubChem Substance
46506514
ChemSpider
4859
BindingDB
19441
RxNav
72143
ChEBI
8772
ChEMBL
CHEMBL81
ZINC
ZINC000000538275
Therapeutic Targets Database
DAP000792
PharmGKB
PA451221
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
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 (286 KB)
MSDS
Download (507 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
1CompletedTreatmentOsteoporosis2
1Not Yet RecruitingTreatmentHealthy Volunteers1
2CompletedPreventionBreast Cancer1
2CompletedPreventionEndometrial Safety / Vasomotor Symptoms1
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentEndometrial Cancer1
2CompletedTreatmentEndometriosis / Pelvic Pain1
2CompletedTreatmentSchizoaffective Disorders / Schizophrenia / Schizophreniform Disorder1
2CompletedTreatmentUrinary Bladder Neoplasms1
2CompletedTreatmentOne to five years postmenopausal1
2WithdrawnTreatmentStage I Prostate Adenocarcinoma / Stage II Prostate Adenocarcinoma1
2, 3CompletedTreatmentAlzheimer's Disease (AD)1
3CompletedPreventionAging / Cognition1
3CompletedPreventionBreast Cancer1
3CompletedPreventionCardiovascular Heart Disease / Neoplasms, Breast1
3CompletedPreventionOsteopenia1
3CompletedPreventionOsteoporosis1
3CompletedTreatmentEndometrial Hyperplasia / Osteoporosis1
3CompletedTreatmentNegative Symptoms of Schizophrenia in Post-menopausal Women1
3CompletedTreatmentPolycystic Ovaries Syndrome1
3CompletedTreatmentPostmenopausal Osteoporosis (PMO)4
3RecruitingTreatmentPsychotic Disorder NOS / Schizoaffective Disorders / Schizophrenia / Schizophreniform Disorder1
3TerminatedNot AvailableOne to five years postmenopausal1
3Unknown StatusTreatmentSchizoaffective Disorders / Schizophrenia1
4CompletedPreventionHealthy Volunteers1
4CompletedTreatmentCompliance / Postmenopausal Osteoporosis (PMO)1
4CompletedTreatmentDepression / Perimenopausal Depression1
4CompletedTreatmentOsteoporosis5
4CompletedTreatmentPostmenopausal Osteoporosis (PMO)5
4CompletedTreatmentSchizoaffective Disorders / Schizophrenia1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenia / Schizophreniform Disorder1
4CompletedTreatmentSchizophrenia2
4RecruitingTreatmentDepressive Syndrome1
4RecruitingTreatmentOsteoporosis / Postmenopausal Osteoporosis (PMO)1
4RecruitingTreatmentSchizoaffective Disorders / Schizophrenia / Schizophreniform Disorder1
4TerminatedPreventionPostmenopausal Osteoporosis (PMO)1
Not AvailableCompletedNot AvailableAdenocarcinomas / Esophageal Cancers / Squamous Cell Carcinoma (SCC)1
Not AvailableCompletedNot AvailableOsteoporosis2
Not AvailableCompletedNot AvailablePostmenopausal Osteoporosis (PMO)1
Not AvailableCompletedPreventionBreast Cancer2
Not AvailableCompletedSupportive CareBreast Cancer / Menopausal Symptoms / Osteoporosis1
Not AvailableCompletedTreatmentBreast Cancer1
Not AvailableNot Yet RecruitingTreatmentRheumatoid Arthritis1
Not AvailableRecruitingNot AvailableSelective Estrogen Receptor Modulator (SERM)1
Not AvailableTerminatedTreatmentPolycystic Ovarian Syndrome1

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Cardinal Health
  • Eli Lilly & Co.
  • Kaiser Foundation Hospital
  • Lilly Del Caribe Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Resource Optimization and Innovation LLC
Dosage forms
FormRouteStrength
TabletOral60 mg/1
Tablet, film coatedOral60 mg
Tablet, film coatedOral60 mg/1
TabletOral
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)
US5393763No1995-02-282012-07-28Us
CA2158400No2006-10-242015-09-15Canada
CA2101356No1998-11-172013-07-27Canada
US6458811No2002-10-012017-03-10Us
US6894064No2005-05-172017-03-10Us
US6797719No2004-09-282017-03-10Us
US8030330No2011-10-042017-03-10Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)268-272MSDS
water solubilityInsolubleMSDS
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
1-benzothiophene / 1-hydroxy-2-unsubstituted benzenoid / 3-aroylthiophene / Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Aryl-phenylketone / Azacycle / Benzenoid / Benzothiophene
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
Humans
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
Humans
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
Humans
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
Humans
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
Humans
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
Humans
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. VandenBrink BM, Davis JA, Pearson JT, Foti RS, Wienkers LC, Rock DA: Cytochrome p450 architecture and cysteine nucleophile placement impact raloxifene-mediated mechanism-based inactivation. Mol Pharmacol. 2012 Nov;82(5):835-42. doi: 10.1124/mol.112.080739. Epub 2012 Aug 2. [PubMed:22859722]
Details
3. Aldehyde oxidase
Kind
Protein
Organism
Humans
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
Humans
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. Fiorelli G, Picariello L, Martineti V, Tonelli F, Brandi ML: Estrogen synthesis in human colon cancer epithelial cells. J Steroid Biochem Mol Biol. 1999 Dec 31;71(5-6):223-30. [PubMed:10704911]
Details
5. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
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. Moore CD, Reilly CA, Yost GS: CYP3A4-Mediated oxygenation versus dehydrogenation of raloxifene. Biochemistry. 2010 Jun 1;49(21):4466-75. doi: 10.1021/bi902213r. [PubMed:20405834]
  2. VandenBrink BM, Davis JA, Pearson JT, Foti RS, Wienkers LC, Rock DA: Cytochrome p450 architecture and cysteine nucleophile placement impact raloxifene-mediated mechanism-based inactivation. Mol Pharmacol. 2012 Nov;82(5):835-42. doi: 10.1124/mol.112.080739. Epub 2012 Aug 2. [PubMed:22859722]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Protein kinase c binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A10
Uniprot ID
Q9HAW8
Uniprot Name
UDP-glucuronosyltransferase 1-10
Molecular Weight
59809.075 Da
References
  1. Kemp DC, Fan PW, Stevens JC: Characterization of raloxifene glucuronidation in vitro: contribution of intestinal metabolism to presystemic clearance. Drug Metab Dispos. 2002 Jun;30(6):694-700. [PubMed:12019197]
  2. Sun D, Jones NR, Manni A, Lazarus P: Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30. doi: 10.1158/1940-6207.CAPR-12-0448. Epub 2013 May 16. [PubMed:23682072]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A8
Uniprot ID
Q9HAW9
Uniprot Name
UDP-glucuronosyltransferase 1-8
Molecular Weight
59741.035 Da
References
  1. Sun D, Jones NR, Manni A, Lazarus P: Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30. doi: 10.1158/1940-6207.CAPR-12-0448. Epub 2013 May 16. [PubMed:23682072]
  2. Kemp DC, Fan PW, Stevens JC: Characterization of raloxifene glucuronidation in vitro: contribution of intestinal metabolism to presystemic clearance. Drug Metab Dispos. 2002 Jun;30(6):694-700. [PubMed:12019197]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Trdan Lusin T, Stieger B, Marc J, Mrhar A, Trontelj J, Zavratnik A, Ostanek B: Organic anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants influence the pharmacokinetics and pharmacodynamics of raloxifene. J Transl Med. 2012 Apr 25;10:76. doi: 10.1186/1479-5876-10-76. [PubMed:22533838]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Trdan Lusin T, Stieger B, Marc J, Mrhar A, Trontelj J, Zavratnik A, Ostanek B: Organic anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants influence the pharmacokinetics and pharmacodynamics of raloxifene. J Transl Med. 2012 Apr 25;10:76. doi: 10.1186/1479-5876-10-76. [PubMed:22533838]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Trdan Lusin T, Mrhar A, Stieger B, Kullak-Ublick GA, Marc J, Ostanek B, Zavratnik A, Kristl A, Berginc K, Delic K, Trontelj J: Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308. doi: 10.1016/j.trsl.2012.03.002. Epub 2012 Mar 28. [PubMed:22683417]
  2. Chang JH, Kochansky CJ, Shou M: The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8. doi: 10.1124/dmd.106.012179. Epub 2006 Sep 7. [PubMed:16959878]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Trdan Lusin T, Mrhar A, Stieger B, Kullak-Ublick GA, Marc J, Ostanek B, Zavratnik A, Kristl A, Berginc K, Delic K, Trontelj J: Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308. doi: 10.1016/j.trsl.2012.03.002. Epub 2012 Mar 28. [PubMed:22683417]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Trdan Lusin T, Mrhar A, Stieger B, Kullak-Ublick GA, Marc J, Ostanek B, Zavratnik A, Kristl A, Berginc K, Delic K, Trontelj J: Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308. doi: 10.1016/j.trsl.2012.03.002. Epub 2012 Mar 28. [PubMed:22683417]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
Molecular Weight
169341.14 Da
References
  1. Trdan Lusin T, Mrhar A, Stieger B, Kullak-Ublick GA, Marc J, Ostanek B, Zavratnik A, Kristl A, Berginc K, Delic K, Trontelj J: Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308. doi: 10.1016/j.trsl.2012.03.002. Epub 2012 Mar 28. [PubMed:22683417]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Zhou X, Wang S, Sun H, Wu B: Sulfonation of raloxifene in HEK293 cells overexpressing SULT1A3: Involvement of breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated protein 4 (MRP4/ABCC4) in excretion of sulfate metabolites. Drug Metab Pharmacokinet. 2015 Dec;30(6):425-33. doi: 10.1016/j.dmpk.2015.09.001. Epub 2015 Oct 9. [PubMed:26611713]

Drug created on June 13, 2005 07:24 / Updated on July 14, 2020 01:57

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