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Showing drug card for Raloxifene (DB00481)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:37
Primary Accession Number DB00481
Secondary Accession Number
  • APRD00400
Name Raloxifene
Drug Type
  • Approved
  • Investigational
  • Small Molecule
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]
Synonyms
  1. LY-139481
  2. RAL
  3. Raloxifene Hcl
  4. Raloxifene Hydrochloride
  5. Raloxifeno [Spanish]
  6. Raloxifenum [Latin]
  7. raloxifene
Brand Names
  1. Evista
  2. Keoxifene
Brand Mixtures Not Available
Chemical IUPAC Name [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone
Chemical Formula C28H27NO4S
Chemical Structure Structure
CAS Registry Number 84449-90-1
InChI Identifier InChI=1/C28H27NO4S/c30-21-8-4-20(5-9-21)28-26(24-13-10-22(31)18-25(24)34-28)27(32)19-6-11-23(12-7-19)33-17-16-29-14-2-1-3-15-29/h4-13,18,30-31H,1-3,14-17H2
InChI Key GZUITABIAKMVPG-UHFFFAOYAG
KEGG Drug Not Available
KEGG Compound C07228 Link Image
PubChem Compound 5035 Link Image
PubChem Substance 148636 Link Image
ChEBI ID Not Available
PharmGKB ID PA451221 Link Image
HET ID RAL Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02239028 Link Image
RxList Link http://www.rxlist.com/cgi/generic/raloxif.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/evi1169.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Raloxifene Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference C. D. Jones et al., J. Med. Cem. 27, 1057(1984)
Average Molecular Weight 473.5830
Monoisotopic Molecular Weight 473.1661
State Solid
Melting Point 143-147oC
Experimental Water Solubility 0.25mg/L Source: PhysProp
Predicted Water Solubility 5.12e-04 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 5.2 Source: PhysProp
Predicted LogP 5.45 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -5.97 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES OC1=CC=C(C=C1)C1=C(C(=O)C2=CC=C(OCCN3CCCCC3)C=C2)C2=C(S1)C=C(O)C=C2
Canonical SMILES OC1=CC=C(C=C1)C1=C(C(=O)C2=CC=C(OCCN3CCCCC3)C=C2)C2=C(S1)C=C(O)C=C2
Drug Category
  • Antihypocalcemic Agents
  • Bone Density Conservation Agents
  • Estrogen Antagonists
  • Osteoporosis Prophylactic
  • Selective Estrogen Receptor Modulators
ATC Codes
AHFS Codes
  • 68:16.12
Indication For the prevention of osteoporosis in post-menopausal women
Pharmacology 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 mammary tissue. Raloxifene decreases bone resorption, increases bone mineral density (BMD) and decreases incidence of fractures. Raloxifene is used in the prevention of postmenopausal osteoporosis and breast cancer.
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. Raloxifene also antagonizes the effects of estrogen on mammary tissue and blocks uterotrophic responses to estrogen.
Absorption Approximately 60% of an oral dose is absorbed, but presystemic glucuronide conjugation is extensive. Absolute bioavailability of raloxifene is 2.0%
Toxicity Not Available
Protein Binding 95%
Biotransformation 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
Half Life 27.7
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Chlorotrianisene Association not recommended
Cholestyramine The resin decreases the effect of raloxifene
Clomifene Association not recommended
Colestipol The resin decreases the effect of raloxifene
Conjugated Estrogens Association not recommended
Diethylstilbestrol Association not recommended
Estradiol Association not recommended
Estriol Association not recommended
Estropipate Association not recommended
Ethinyl Estradiol Association not recommended
Levothyroxine Raloxifene decreases absorption of levothyroxine
Mestranol Association not recommended
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.
Pathways Not Available
General References
  1. Barrett-Connor E: Raloxifene: risks and benefits. Ann N Y Acad Sci. 2001 Dec;949:295-303. [PubMed Link Image]
  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 Link Image]
  3. : A STARring role for raloxifene? Lancet Oncol. 2006 Jun;7(6):443. [PubMed Link Image]
  4. Drugs.com Link Image
  5. Wikipedia Link Image
  6. RxList Link Image
  7. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Aldehyde oxidase
Targets
  1. Estrogen receptor
  2. Estrogen receptor beta
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Aldehyde oxidase
Enzyme 1 Gene Name AOX1
Enzyme 1 SwissProt ID Q06278 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|Q06278|ADO_HUMAN Aldehyde oxidase (EC 1.2.3.1) 
MDRASELLFYVNGRKVIEKNVDPETMLLPYLRKKLRLTGTPYGCGGGGCGACTVMISRYN
PITKRIRHHPANACLIPICSLYGAAVTTVEGIGSTHTRIHPVQERIAKCHGTQCGFCTPG
MVMSIYPLLRNHPEPTLDQLTDALGGNLCRCHGYRPIIDACKTFCKTSGCCQSKENGVCC
LDQGINGLPEFEEGSKTSPKLFAEEEFLPLDPTQELIFPPELMIMADKQSQRTRVFGSER
MMWFSPVTLKDLLEFKFKYPQAPVIMGNTSVGPEVKFKGVFHPGYNSPDRIEEPECCKPC
IYGLTLGAGLSLAQVKDILADVVQKLPEEKTQMYHALLKHLGTLAGSQIRNMASLGGHII
SRHPDSDLNPILAVGNCTLNLLSKEGKRQIPLNEQFLSKCPNADLKPQEILVSVNIPISR
KWEFVSAFRQAQRQENALAIVNSGMRVFFGEGDGIIRELCISYGGVGPATICAKNSCQKL
IGRHWNEQMLDIACRLILNEVSLLGSAPGGKVEFKRTLIISFLFKFYLEVSQILKKMDPV
HYPSLADKYESALEDLHSKHHCSTLKYQNIGPKQHPEDPIGHPIMHLSGVKHATGEAIYC
DDMPLVDQELFLTFVTSSRAHAKIVSIDLSEALSMPGVVDIMTAEHLSDVNSFCFFTEAE
KFLATDKVFCVGQLVCAVLADSEVQAKRAAKRVKIVYQDLEPLILTIEESIQHNSSFKPE
RKLEYGNVDEAFKVVDQILEGEIHMGGQEHFYMETQSMLVVPKGEDQEMDVYVSTQFPKY
IQDIVASTLKLPANKVMCHVRRVGGAFGGKVLKTGIIAAVTAFAANKHGRAVRCVLERGE
DMLITGGRHPYLGKYKAGFMNDGRILALDMEHYSNAGASLDESLFVIEMGLLKMDNAYKF
PNLRCRGWACRTNLPSNTAFRGFGFPQAVLITESCITEVAAKCGLSPEKVRIINMYKEID
QTPYKQEINAKNLIQCWRECMAMSSYSLRKVAVEKFNAENYWKKKGLAMVPLKFPVGLAS
RAAGQAAALVHIYLDGSVLVTHGGIEMGQGVHTKMIQVVSRELRMPMSNVHLRGTSTETV
PNANISGGSVVADLNGLAVKDACQTLLKRLEPIISKNPKGTWKDWAQTAFDESINLSAVG
YFRGYESDMNWEKGEGQPFEYFVYGAACSEVEIDCLTGDHKNIRTDIVMDVGCSINPAID
IGQIEGAFIQGMGLYTIEELNYSPQGILHTRGPDQYKIPAICDMPTELHIALLPPSQNSN
TLYSSKGLGESGVFLGCSVFFAIHDAVSAARQERGLHGPLTLNSPLTPEKIRMACEDKFT
KMIPRDEPGSYVPWNVPI
Drug Target 1 [top]
Target 1 ID 136
Target 1 Name Estrogen receptor
Target 1 Synonyms
  1. ER
  2. ER-alpha
  3. Estradiol receptor
Target 1 Gene Name ESR1
Target 1 Protein Sequence >Estrogen receptor 
MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAY
EFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPF
LQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAK
ETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQAC
RLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKR
SKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINW
AKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEG
MVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLD
KITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLL
LEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
Target 1 Number of Residues 604
Target 1 Molecular Weight 66217
Target 1 Theoretical pI 8.14
Target 1 GO Classification
Function
ion binding
cation binding
transition metal ion binding
zinc ion binding
steroid binding
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 1 General Function Involved in transcription factor activity
Target 1 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
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 31234 Link Image
Target 1 UniProtKB/Swiss-Prot ID P03372 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ESR1_HUMAN Link Image
Target 1 PDB ID 1R5K Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Nucleus
Target 1 Gene Sequence >1788 bp 
ATGACCATGACCCTCCACACCAAAGCATCTGGGATGGCCCTACTGCATCAGATCCAAGGG
AACGAGCTGGAGCCCCTGAACCGTCCGCAGCTCAAGATCCCCCTGGAGCGGCCCCTGGGC
GAGGTGTACCTGGACAGCAGCAAGCCCGCCGTGTACAACTACCCCGAGGGCGCCGCCTAC
GAGTTCAACGCCGCGGCCGCCGCCAACGCGCAGGTCTACGGTCAGACCGGCCTCCCCTAC
GGCCCCGGGTCTGAGGCTGCGGCGTTCGGCTCCAACGGCCTGGGGGGTTTCCCCCCACTC
AACAGCGTGTCTCCGAGCCCGCTGATGCTACTGCACCCGCCGCCGCAGCTGTCGCCTTTC
CTGCAGCCCCACGGCCAGCAGGTGCCCTACTACCTGGAGAACGAGCCCAGCGGCTACACG
GTGCGCGAGGCCGGCCCGCCGGCATTCTACAGGCCAAATTCAGATAATCGACGCCAGGGT
GGCAGAGAAAGATTGGCCAGTACCAATGACAAGGGAAGTATGGCTATGGAATCTGCCAAG
GAGACTCGCTACTGTGCAGTGTGCAATGACTATGCTTCAGGCTACCATTATGGAGTCTGG
TCCTGTGAGGGCTGCAAGGCCTTCTTCAAGAGAAGTATTCAAGGACATAACGACTATATG
TGTCCAGCCACCAACCAGTGCACCATTGATAAAAACAGGAGGAAGAGCTGCCAGGCCTGC
CGGCTCCGCAAATGCTACGAAGTGGGAATGATGAAAGGTGGGATACGAAAAGACCGAAGA
GGAGGGAGAATGTTGAAACACAAGCGCCAGAGAGATGATGGGGAGGGCAGGGGTGAAGTG
GGGTCTGCTGGAGACATGAGAGCTGCCAACCTTTGGCCAAGCCCGCTCATGATCAAACGC
TCTAAGAAGAACAGCCTGGCCTTGTCCCTGACGGCCGACCAGATGGTCAGTGCCTTGTTG
GATGCTGAGCCCCCCATACTCTATTCCGAGTATGATCCTACCAGACCCTTCAGTGAAGCT
TCGATGATGGGCTTACTGACCAACCTGGCAGACAGGGAGCTGGTTCACATGATCAACTGG
GCGAAGAGGGTGCCAGGCTTTGTGGATTTGACCCTCCATGATCAGGTCCACCTTCTAGAA
TGTGCCTGGCTAGAGATCCTGATGATTGGTCTCGTCTGGCGCTCCATGGAGCACCCAGTG
AAGCTACTGTTTGCTCCTAACTTGCTCTTGGACAGGAACCAGGGAAAATGTGTAGAGGGC
ATGGTGGAGATCTTCGACATGCTGCTGGCTACATCATCTCGGTTCCGCATGATGAATCTG
CAGGGAGAGGAGTTTGTGTGCCTCAAATCTATTATTTTGCTTAATTCTGGAGTGTACACA
TTTCTGTCCAGCACCCTGAAGTCTCTGGAAGAGAAGGACCATATCCACCGAGTCCTGGAC
AAGATCACAGACACTTTGATCCACCTGATGGCCAAGGCAGGCCTGACCCTGCAGCAGCAG
CACCAGCGGCTGGCCCAGCTCCTCCTCATCCTCTCCCACATCAGGCACATGAGTAACAAA
GGCATGGAGCATCTGTACAGCATGAAGTGCAAGAACGTGGTGCCCCTCTATGACCTGCTG
CTGGAGATGCTGGACGCCCACCGCCTACATGCGCCCACTAGCCGTGGAGGGGCATCCGTG
GAGGAGACGGACCAAAGCCACTTGGCCACTGCGGGCTCTACTTCATCGCATTCCTTGCAA
AAGTATTACATCACGGGGGAGGCAGAGGGTTTCCCTGCCACAGTCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ESR1 Link Image
Target 1 GenAtlas ID ESR1 Link Image
Target 1 HGNC ID HGNC:3467 Link Image
Target 1 Chromosome Location 6
Target 1 Locus 6q25.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS: An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6947-52. [PubMed Link Image]
  2. Rogatsky I, Trowbridge JM, Garabedian MJ: Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex. J Biol Chem. 1999 Aug 6;274(32):22296-302. [PubMed Link Image]
  3. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW: A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J Biol Chem. 1999 Nov 26;274(48):34283-93. [PubMed Link Image]
  4. Schubert EL, Lee MK, Newman B, King MC: Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene and breast cancer susceptibility. J Steroid Biochem Mol Biol. 1999 Nov;71(1-2):21-7. [PubMed Link Image]
  5. Sauve F, McBroom LD, Gallant J, Moraitis AN, Labrie F, Giguere V: CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Mol Cell Biol. 2001 Jan;21(1):343-53. [PubMed Link Image]
  6. Shao W, Halachmi S, Brown M: ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol. 2002 May;22(10):3358-72. [PubMed Link Image]
  7. Wong CW, McNally C, Nickbarg E, Komm BS, Cheskis BJ: Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14783-8. Epub 2002 Nov 1. [PubMed Link Image]
  8. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed Link Image]
  9. Reese JC, Katzenellenbogen BS: Characterization of a temperature-sensitive mutation in the hormone binding domain of the human estrogen receptor. Studies in cell extracts and intact cells and their implications for hormone-dependent transcriptional activation. J Biol Chem. 1992 May 15;267(14):9868-73. [PubMed Link Image]
  10. Schwabe JW, Neuhaus D, Rhodes D: Solution structure of the DNA-binding domain of the oestrogen receptor. Nature. 1990 Nov 29;348(6300):458-61. [PubMed Link Image]
  11. 2792078 Tora L, Mullick A, Metzger D, Ponglikitmongkol M, Park I, Chambon P: The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J. 1989 Jul;8(7):1981-6.
  12. 3753802 Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J: Sequence and expression of human estrogen receptor complementary DNA. Science. 1986 Mar 7;231(4742):1150-4.
  13. 3754034 Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P: Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13-19;320(6058):134-9.
  14. 7476978 Joel PB, Traish AM, Lannigan DA: Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Mol Endocrinol. 1995 Aug;9(8):1041-52.
  15. 7539106 Arnold SF, Obourn JD, Jaffe H, Notides AC: Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vitro. Mol Endocrinol. 1995 Jan;9(1):24-33.
  16. 7838153 Arnold SF, Obourn JD, Jaffe H, Notides AC: Serine 167 is the major estradiol-induced phosphorylation site on the human estrogen receptor. Mol Endocrinol. 1994 Sep;8(9):1208-14.
  17. 7916651 Pfeffer U, Fecarotta E, Castagnetta L, Vidali G: Estrogen receptor variant messenger RNA lacking exon 4 in estrogen-responsive human breast cancer cell lines. Cancer Res. 1993 Feb 15;53(4):741-3.
  18. 8221895 Schwabe JW, Chapman L, Finch JT, Rhodes D: The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements. Cell. 1993 Nov 5;75(3):567-78.
  19. 8600466 Pink JJ, Wu SQ, Wolf DM, Bilimoria MM, Jordan VC: A novel 80 kDa human estrogen receptor containing a duplication of exons 6 and 7. Nucleic Acids Res. 1996 Mar 1;24(5):962-9.
  20. 8961262 McInerney EM, Ince BA, Shapiro DJ, Katzenellenbogen BS: A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action. Mol Endocrinol. 1996 Dec;10(12):1519-26.
  21. 9195227 Anderson TI, Wooster R, Laake K, Collins N, Warren W, Skrede M, Elles R, Tveit KM, Johnston SR, Dowsett M, Olsen AO, Moller P, Stratton MR, Borresen-Dale AL: Screening for ESR mutations in breast and ovarian cancer patients. Hum Mutat. 1997;9(6):531-6.
  22. 9338790 Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M: Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997 Oct 16;389(6652):753-8.
  23. 9600906 Tanenbaum DM, Wang Y, Williams SP, Sigler PB: Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains. Proc Natl Acad Sci U S A. 1998 May 26;95(11):5998-6003.
  24. 9619507 Maalouf GJ, Xu W, Smith TF, Mohr SC: Homology model for the ligand-binding domain of the human estrogen receptor. J Biomol Struct Dyn. 1998 Apr;15(5):841-51.
  25. 9875847 Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL: The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 1998 Dec 23;95(7):927-37.
Target 1 Drug References
  1. Khovidhunkit W, Shoback DM: Clinical effects of raloxifene hydrochloride in women. Ann Intern Med. 1999 Mar 2;130(5):431-9. [PubMed Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 869
Target 2 Name Estrogen receptor beta
Target 2 Synonyms
  1. ER-beta
Target 2 Gene Name ESR2
Target 2 Protein Sequence >Estrogen receptor beta 
MDIKNSPSSLNSPSSYNCSQSILPLEHGSIYIPSSYVDSHHEYPAMTFYSPAVMNYSIPS
NVTNLEGGPGRQTTSPNVLWPTPGHLSPLVVHRQLSHLYAEPQKSPWCEARSLEHTLPVN
RETLKRKVSGNRCASPVTGPGSKRDAHFCAVCSDYASGYHYGVWSCEGCKAFFKRSIQGH
NDYICPATNQCTIDKNRRKSCQACRLRKCYEVGMVKCGSRRERCGYRLVRRQRSADEQLH
CAGKAKRSGGHAPRVRELLLDALSPEQLVLTLLEAEPPHVLISRPSAPFTEASMMMSLTK
LADKELVHMISWAKKIPGFVELSLFDQVRLLESCWMEVLMMGLMWRSIDHPGKLIFAPDL
VLDRDEGKCVEGILEIFDMLLATTSRFRELKLQHKEYLCVKAMILLNSSMYPLVTATQDA
DSSRKLAHLLNAVTDALVWVIAKSGISSQQQSMRLANLLMLLSHVRHASNKGMEHLLNMK
CKNVVPVYDLLLEMLNAHVLRGCKSSITGSECSPAEDSKSKEGSQNPQSQ
Target 2 Number of Residues 538
Target 2 Molecular Weight 59217
Target 2 Theoretical pI 8.55
Target 2 GO Classification
Function
ion binding
cation binding
transition metal ion binding
zinc ion binding
steroid binding
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 2 General Function Involved in transcription factor activity
Target 2 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. 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 ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 2911152 Link Image
Target 2 UniProtKB/Swiss-Prot ID Q92731 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name ESR2_HUMAN Link Image
Target 2 PDB ID 1QKM Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Nucleus
Target 2 Gene Sequence >1593 bp 
ATGGATATAAAAAACTCACCATCTAGCCTTAATTCTCCTTCCTCCTACAACTGCAGTCAA
TCCATCTTACCCCTGGAGCACGGCTCCATATACATACCTTCCTCCTATGTAGACAGCCAC
CATGAATATCCAGCCATGACATTCTATAGCCCTGCTGTGATGAATTACAGCATTCCCAGC
AATGTCACTAACTTGGAAGGTGGGCCTGGTCGGCAGACCACAAGCCCAAATGTGTTGTGG
CCAACACCTGGGCACCTTTCTCCTTTAGTGGTCCATCGCCAGTTATCACATCTGTATGCG
GAACCTCAAAAGAGTCCCTGGTGTGAAGCAAGATCGCTAGAACACACCTTACCTGTAAAC
AGAGAGACACTGAAAAGGAAGGTTAGTGGGAACCGTTGCGCCAGCCCTGTTACTGGTCCA
GGTTCAAAGAGGGATGCTCACTTCTGCGCTGTCTGCAGCGATTACGCATCGGGATATCAC
TATGGAGTCTGGTCGTGTGAAGGATGTAAGGCCTTTTTTAAAAGAAGCATTCAAGGACAT
AATGATTATATTTGTCCAGCTACAAATCAGTGTACAATCGATAAAAACCGGCGCAAGAGC
TGCCAGGCCTGCCGACTTCGGAAGTGTTACGAAGTGGGAATGGTGAAGTGTGGCTCCCGG
AGAGAGAGATGTGGGTACCGCCTTGTGCGGAGACAGAGAAGTGCCGACGAGCAGCTGCAC
TGTGCCGGCAAGGCCAAGAGAAGTGGCGGCCACGCGCCCCGAGTGCGGGAGCTGCTGCTG
GACGCCCTGAGCCCCGAGCAGCTAGTGCTCACCCTCCTGGAGGCTGAGCCGCCCCATGTG
CTGATCAGCCGCCCCAGTGCGCCCTTCACCGAGGCCTCCATGATGATGTCCCTGACCAAG
TTGGCCGACAAGGAGTTGGTACACATGATCAGCTGGGCCAAGAAGATTCCCGGCTTTGTG
GAGCTCAGCCTGTTCGACCAAGTGCGGCTCTTGGAGAGCTGTTGGATGGAGGTGTTAATG
ATGGGGCTGATGTGGCGCTCAATTGACCACCCCGGCAAGCTCATCTTTGCTCCAGATCTT
GTTCTGGACAGGGATGAGGGGAAATGCGTAGAAGGAATTCTGGAAATCTTTGACATGCTC
CTGGCAACTACTTCAAGGTTTCGAGAGTTAAAACTCCAACACAAAGAATATCTCTGTGTC
AAGGCCATGATCCTGCTCAATTCCAGTATGTACCCTCTGGTCACAGCGACCCAGGATGCT
GACAGCAGCCGGAAGCTGGCTCACTTGCTGAACGCCGTGACCGATGCTTTGGTTTGGGTG
ATTGCCAAGAGCGGCATCTCCTCCCAGCAGCAATCCATGCGCCTGGCTAACCTCCTGATG
CTCCTGTCCCACGTCAGGCATGCGAGTAACAAGGGCATGGAACATCTGCTCAACATGAAG
TGCAAAAATGTGGTCCCAGTGTATGACCTGCTGCTGGAGATGCTGAATGCCCACGTGCTT
CGCGGGTGCAAGTCCTCCATCACGGGGTCCGAGTGCAGCCCGGCAGAGGACAGTAAAAGC
AAAGAGGGCTCCCAGAACCCACAGTCTCAGTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID ESR2 Link Image
Target 2 GenAtlas ID ESR2 Link Image
Target 2 HGNC ID HGNC:3468 Link Image
Target 2 Chromosome Location 14
Target 2 Locus 14q23.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Caira F, Antonson P, Pelto-Huikko M, Treuter E, Gustafsson JA: Cloning and characterization of RAP250, a novel nuclear receptor coactivator. J Biol Chem. 2000 Feb 25;275(8):5308-17. [PubMed Link Image]
  2. Li LC, Yeh CC, Nojima D, Dahiya R: Cloning and characterization of human estrogen receptor beta promoter. Biochem Biophys Res Commun. 2000 Aug 28;275(2):682-9. [PubMed Link Image]
  3. Sauve F, McBroom LD, Gallant J, Moraitis AN, Labrie F, Giguere V: CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Mol Cell Biol. 2001 Jan;21(1):343-53. [PubMed Link Image]
  4. Wong CW, McNally C, Nickbarg E, Komm BS, Cheskis BJ: Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14783-8. Epub 2002 Nov 1. [PubMed Link Image]
  5. Mosselman S, Polman J, Dijkema R: ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 1996 Aug 19;392(1):49-53. [PubMed Link Image]
  6. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM: Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569-80. [PubMed Link Image]
  7. Pace P, Taylor J, Suntharalingam S, Coombes RC, Ali S: Human estrogen receptor beta binds DNA in a manner similar to and dimerizes with estrogen receptor alpha. J Biol Chem. 1997 Oct 10;272(41):25832-8. [PubMed Link Image]
  8. Ogawa S, Inoue S, Watanabe T, Hiroi H, Orimo A, Hosoi T, Ouchi Y, Muramatsu M: The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro. Biochem Biophys Res Commun. 1998 Feb 4;243(1):122-6. [PubMed Link Image]
  9. Moore JT, McKee DD, Slentz-Kesler K, Moore LB, Jones SA, Horne EL, Su JL, Kliewer SA, Lehmann JM, Willson TM: Cloning and characterization of human estrogen receptor beta isoforms. Biochem Biophys Res Commun. 1998 Jun 9;247(1):75-8. [PubMed Link Image]
  10. Ogawa S, Inoue S, Watanabe T, Orimo A, Hosoi T, Ouchi Y, Muramatsu M: Molecular cloning and characterization of human estrogen receptor betacx: a potential inhibitor ofestrogen action in human. Nucleic Acids Res. 1998 Aug 1;26(15):3505-12. [PubMed Link Image]
  11. 9685228 Lu B, Leygue E, Dotzlaw H, Murphy LJ, Murphy LC, Watson PH: Estrogen receptor-beta mRNA variants in human and murine tissues. Mol Cell Endocrinol. 1998 Mar 16;138(1-2):199-203.
Target 2 Drug 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 Link Image]
  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 Link Image]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  4. 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 Link Image]
  5. 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 Link Image]
  6. 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 Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.