DGIdb - RALOXIFENE Drug Record

RALOXIFENE chembl:CHEMBL81 Approved

Alternate Names:

J22.982B
EVISTA
LY-139481
RALOXIFENE
(2-(4-HYDROXYPHENYL)-6-HYDROXYBENZO(B)THIEN-3-YL)(4-(2-(1-PIPERIDINYL)ETHOXY)PHENYL)METHANONE
LY 139481
LY-156758
RALOXIFÈNE
RALOXIFENUM
RALOXIFENO
pubchem.compound:5035
chembl:CHEMBL81
drugbank:00481
chemidplus:84449-90-1
rxcui:72143

Drug Info:

FDA Approval	1997
Drug Class	small molecule
Drug Indications	Hormone Replacement Agents
Drug Class	hormone replacement agents
Year of Approval	1997

(4 More Sources)

Publications:

Matsumoto, 2006, [Selective estrogen receptor modulators (SERMs)]., Clin Calcium
Moen et al., 2008, Raloxifene: a review of its use in the prevention of invasive breast cancer., Drugs
Bryant et al., An estrogen receptor basis for raloxifene action in bone., J. Steroid Biochem. Mol. Biol.
Khovidhunkit et al., 1999, Clinical effects of raloxifene hydrochloride in women., Ann. Intern. Med.
Scott et al., 1999, Raloxifene: a selective estrogen receptor modulator., Am Fam Physician
Schafer et al., 1999, The interaction of raloxifene and the active metabolite of the antiestrogen EM-800 (SC 5705) with the human estrogen receptor., Cancer Res.
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Figtree et al., 1999, Raloxifene acutely relaxes rabbit coronary arteries in vitro by an estrogen receptor-dependent and nitric oxide-dependent mechanism., Circulation
Cummings et al., 1999, The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation., JAMA
Labad J et al., 2016, Pharmacogenetic study of the effects of raloxifene on negative symptoms of postmenopausal women with schizophrenia: A double-blind, randomized, placebo-controlled trial., Eur Neuropsychopharmacol
Jain D et al., 2010, A mutant selective anti-estrogen is a pure antagonist on EREs and AP-1 response elements., Bioorg Med Chem Lett
Lambrinoudaki et al., 2008, Circulating leptin and ghrelin are differentially influenced by estrogen/progestin therapy and raloxifene., Maturitas
Sakatis MZ et al., 2012, Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds., Chem Res Toxicol
Li P et al., 2011, A refined cytochrome P540 IC₅₀ shift assay for reliably identifying CYP3A time-dependent inhibitors., Drug Metab Dispos
Foti RS et al., 2011, Mechanism-based inactivation of cytochrome P450 3A4 by mibefradil through heme destruction., Drug Metab Dispos
Du et al., 2004, Both estrogen and raloxifene protect against beta-amyloid-induced neurotoxicity in estrogen receptor alpha-transfected PC12 cells by activation of telomerase activity via Akt cascade., J. Endocrinol.
Duntas et al., 2001, Lack of substantial effects of raloxifene on thyroxine-binding globulin in postmenopausal women: dependency on thyroid status., Thyroid
Zhou et al., 2002, Selective estrogen receptor modulator effects in the rat brain., Neuroendocrinology
Sun et al., 2002, Antagonists selective for estrogen receptor alpha., Endocrinology
Kim et al., 2002, Raloxifene, a selective estrogen receptor modulator, induces apoptosis in androgen-responsive human prostate cancer cell line LNCaP through an androgen-independent pathway., Cancer Res.
Iannone et al., 2001, Multiplexed molecular interactions of nuclear receptors using fluorescent microspheres., Cytometry
Surazynski et al., 2003, Differential effects of estradiol and raloxifene on collagen biosynthesis in cultured human skin fibroblasts., Int. J. Mol. Med.
Simoncini et al., 2002, Nongenomic mechanisms of endothelial nitric oxide synthase activation by the selective estrogen receptor modulator raloxifene., Circulation
Li H et al., 2014, Drug design targeting protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning: discovery of raloxifene and bazedoxifene as novel inhibitors of IL-6/GP130 interface., J Med Chem
Cheung et al., 2003, Interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin production by human osteoblastic cells: comparison of the effects of 17-beta oestradiol and raloxifene., J. Endocrinol.
Ingle JN et al., 2013, Selective estrogen receptor modulators and pharmacogenomic variation in ZNF423 regulation of BRCA1 expression: individualized breast cancer prevention., Cancer Discov
Tena-Sempere et al., 2004, Mechanisms for altered reproductive function in female rats following neonatal administration of raloxifene., Eur. J. Endocrinol.
Ozeren et al., 2005, The effects of short-term raloxifene therapy on fibrinolysis markers: TAFI, tPA, and PAI-1., Acta Obstet Gynecol Scand
Oviedo et al., Raloxifene increases the capacity of serum to promote prostacyclin release in human endothelial cells: implication of COX-1 and COX-2., Menopause
Ciotti M et al., 1999, Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) by the human UDP-glucuronosyltransferases encoded at the UGT1 locus., Biochem Biophys Res Commun
Hu ZY et al., 2010, Dose-dependent association between UGT1A1*28 genotype and irinotecan-induced neutropenia: low doses also increase risk., Clin Cancer Res
Ramesh et al., 2010, Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives., Biomed. Chromatogr.
Onoue M et al., 2009, UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients., Int J Clin Oncol
Cecchin E et al., 2009, Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan., J Clin Oncol
Obradovic M et al., 2008, Cost-effectiveness of UGT1A1 genotyping in second-line, high-dose, once every 3 weeks irinotecan monotherapy treatment of colorectal cancer., Pharmacogenomics
Lankisch TO et al., 2008, Gilbert's Syndrome and irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk., Cancer Epidemiol Biomarkers Prev
Hoskins JM et al., 2007, UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters., J Natl Cancer Inst
Lankisch TO et al., 2006, Gilbert's disease and atazanavir: from phenotype to UDP-glucuronosyltransferase haplotype., Hepatology
Kawato Y et al., 1991, Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11., Cancer Res
Danoff TM et al., 2004, A Gilbert's syndrome UGT1A1 variant confers susceptibility to tranilast-induced hyperbilirubinemia., Pharmacogenomics J
Kishi S et al., 2004, Effects of prednisone and genetic polymorphisms on etoposide disposition in children with acute lymphoblastic leukemia., Blood
Gagné JF et al., 2002, Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38)., Mol Pharmacol
Kemp DC et al., 2002, Characterization of raloxifene glucuronidation in vitro: contribution of intestinal metabolism to presystemic clearance., Drug Metab Dispos
Guillemette C et al., 2000, Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGT1A7 gene., Pharmacogenetics
Mossetti G et al., 2008, Vitamin D receptor gene polymorphisms predict acquired resistance to clodronate treatment in patients with Paget's disease of bone., Calcif Tissue Int
Otrock ZK et al., 2008, Vitamin D receptor genotypes and response to zoledronic acid therapy in thalassemia-induced osteoporosis., Ann Hematol
Palomba S et al., 2005, BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial., Osteoporos Int
Palomba et al., 2003, Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes., Clin. Endocrinol. (Oxf)
Tofteng CL et al., 2002, Two polymorphisms in the vitamin D receptor gene--association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish Osteoporosis Prevention Study., J Bone Miner Res
Marc J et al., 1999, VDR genotype and response to etidronate therapy in late postmenopausal women., Osteoporos Int

RALOXIFENE ZNF423

Interaction Score: 2.13

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
23764426

Sources:
PharmGKB
RALOXIFENE IL6ST

Interaction Score: 1.42

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24456369

Sources:
DTC
RALOXIFENE UGT1A1

Interaction Score: 0.92

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
10381366 20562211 19852077 19390945 19364970 18466101 18349289 17728214 17058217 1651156 14647407 12969965 12181437 12019197 11037804

Sources:
PharmGKB
RALOXIFENE PLAT

Interaction Score: 0.53

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
16167916

Sources:
NCI
RALOXIFENE IL6R

Interaction Score: 0.47

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
24456369

Sources:
DTC
RALOXIFENE GNRH1

Interaction Score: 0.39

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15012627

Sources:
NCI
RALOXIFENE UGT1A8

Interaction Score: 0.39

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
27546373

Sources:
PharmGKB
RALOXIFENE TSHB

Interaction Score: 0.39

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11525272

Sources:
NCI
RALOXIFENE ESR2

Interaction Score: 0.38

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
20659801 11810032 10418979 11861516 11752352 12097269 11500849

Sources:
DTC TdgClinicalTrial TEND PharmGKB
RALOXIFENE GHRL

Interaction Score: 0.36

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
18164562

Sources:
NCI
RALOXIFENE TERT

Interaction Score: 0.19

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15590986

Sources:
NCI
RALOXIFENE ESR1

Interaction Score: 0.19

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16951478 18778124 10418979 10068418 10507743 10485477 11752352 10477535 10376571 27546373 20659801

Sources:
DTC TdgClinicalTrial TEND PharmGKB TTD FDA
RALOXIFENE IL1B

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
12773123

Sources:
NCI
RALOXIFENE IGF1R

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
14533013

Sources:
NCI
RALOXIFENE PTGS2

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
15243281

Sources:
NCI
RALOXIFENE PIK3CG

Interaction Score: 0.05

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11901050

Sources:
NCI
RALOXIFENE VDR

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
19020788 18443790 15739035 12608943 12162507 10692979

Sources:
PharmGKB
RALOXIFENE PIK3CA

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
11901050

Sources:
NCI
RALOXIFENE THPO

Interaction Score: 0.03

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
RALOXIFENE CBX1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
RALOXIFENE CYP3A4

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
21393461 21447734 22931300

Sources:
DTC
RALOXIFENE CYP2C19

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22931300

Sources:
DTC
RALOXIFENE ATXN2

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
RALOXIFENE CYP1A2

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22931300

Sources:
DTC
RALOXIFENE CYP2D6

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
22931300

Sources:
DTC
RALOXIFENE TP53

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
RALOXIFENE ALDH1A1

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
RALOXIFENE HSD17B10

Interaction Score: 0.01

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC
RALOXIFENE MAPT

Interaction Score: 0.0

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
None found

Sources:
DTC

TEND: RALOXIFENE
- Version: 01-August-2011
Alternate Names:

RALOXIFENE Primary Drug Name

Drug Info:

Year of Approval 1997

Drug Class hormone replacement agents

Publications:
TdgClinicalTrial: RALOXIFENE
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications Hormone Replacement Agents

Drug Class small molecule

FDA Approval 1997

Publications:

DTC: RALOXIFENE

Version: 02-September-2020

Alternate Names:

CHEMBL81 ChEMBL Drug ID

Drug Info:

Publications:

Jain D et al., 2010, A mutant selective anti-estrogen is a pure antagonist on EREs and AP-1 response elements., Bioorg Med Chem Lett

Sakatis MZ et al., 2012, Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds., Chem Res Toxicol

Li P et al., 2011, A refined cytochrome P540 IC₅₀ shift assay for reliably identifying CYP3A time-dependent inhibitors., Drug Metab Dispos

NCI: RALOXIFENE

Version: 14-September-2017

Alternate Names:

C1518 NCI drug code

Drug Info:

Publications:

Duntas et al., 2001, Lack of substantial effects of raloxifene on thyroxine-binding globulin in postmenopausal women: dependency on thyroid status., Thyroid

Tena-Sempere et al., 2004, Mechanisms for altered reproductive function in female rats following neonatal administration of raloxifene., Eur. J. Endocrinol.

Surazynski et al., 2003, Differential effects of estradiol and raloxifene on collagen biosynthesis in cultured human skin fibroblasts., Int. J. Mol. Med.

PharmGKB: raloxifene

Version: 18-August-2020

Alternate Names:

Drug Info:

Publications:

Cecchin E et al., 2009, Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan., J Clin Oncol

Ramesh et al., 2010, Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives., Biomed. Chromatogr.

Lankisch TO et al., 2008, Gilbert's Syndrome and irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk., Cancer Epidemiol Biomarkers Prev

TTD: Raloxifene
- Version: 2020.06.01
Alternate Names:

D01XBA TTD Drug ID

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL81
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
FDA: Raloxifene
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:

agonist (activating)
antagonist (inhibitory)

Novel drug target	Established target
Trial Name	-

agonist (activating)
antagonist (inhibitory)

Trial Name	-
Novel drug target	Established target

RALOXIFENE Drug Record

RALOXIFENE chembl:CHEMBL81 Approved

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 23764426

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24456369

Sources: DTC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 10381366 20562211 19852077 19390945 19364970 18466101 18349289 17728214 17058217 1651156 14647407 12969965 12181437 12019197 11037804

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 16167916

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 24456369

Sources: DTC

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 15012627

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 27546373

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 11525272

Sources: NCI

Interaction Types & Directionality: agonist (activating) antagonist (inhibitory)

Interaction Info: Novel drug target Established target Trial Name -

PMIDs: 20659801 11810032 10418979 11861516 11752352 12097269 11500849

Sources: DTC TdgClinicalTrial TEND PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 18164562

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 15590986

Sources: NCI

Interaction Types & Directionality: agonist (activating) antagonist (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target

PMIDs: 16951478 18778124 10418979 10068418 10507743 10485477 11752352 10477535 10376571 27546373 20659801

Sources: DTC TdgClinicalTrial TEND PharmGKB TTD FDA

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 12773123

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 14533013

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 15243281

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 11901050

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 19020788 18443790 15739035 12608943 12162507 10692979

Sources: PharmGKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 11901050

Sources: NCI

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: None found

Interaction Types & Directionality:

n/a

PMIDs:
23764426

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
24456369

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
10381366 20562211 19852077 19390945 19364970 18466101 18349289 17728214 17058217 1651156 14647407 12969965 12181437 12019197 11037804

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
16167916

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
24456369

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
15012627

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
27546373

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
11525272

Sources:
NCI

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

PMIDs:
20659801 11810032 10418979 11861516 11752352 12097269 11500849

Sources:
DTC TdgClinicalTrial TEND PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
18164562

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
15590986

Sources:
NCI

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

PMIDs:
16951478 18778124 10418979 10068418 10507743 10485477 11752352 10477535 10376571 27546373 20659801

Sources:
DTC TdgClinicalTrial TEND PharmGKB TTD FDA

Interaction Types & Directionality:

n/a

PMIDs:
12773123

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
14533013

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
15243281

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
11901050

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
19020788 18443790 15739035 12608943 12162507 10692979

Sources:
PharmGKB

Interaction Types & Directionality:

n/a

PMIDs:
11901050

Sources:
NCI

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
21393461 21447734 22931300

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
22931300

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
22931300

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
22931300

Sources:
DTC

Interaction Types & Directionality:

n/a

PMIDs:
None found

Sources:
DTC