| Revision as of 13:58, 28 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,071 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEMBL', 'CASNo').← Previous edit |
Latest revision as of 15:16, 19 January 2025 edit undoOzzie10aaaa (talk | contribs)Autopatrolled, Extended confirmed users, New page reviewers214,204 editsm Cleaned up using AutoEd |
| (35 intermediate revisions by 23 users not shown) |
| Line 1: |
Line 1: |
|
|
{{Short description|Chemical compound}} |
|
{{chembox |
|
|
|
{{Drugbox |
|
|
| Verifiedfields = changed |
|
|
| Watchedfields = changed |
|
|
| verifiedrevid = 457819279 |
|
|
| IUPAC_name = 2-(4-Methoxyphenyl)-3--1-benzothiophen-6-ol |
|
|
| image = Arzoxifene.svg |
|
|
| width = 250px |
|
|
|
|
|
<!--Clinical data--> |
|
|
| tradename = |
|
|
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
|
|
| pregnancy_US = <!-- A / B / C / D / X --> |
|
|
| pregnancy_category = |
|
|
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
|
|
| legal_CA = |
|
|
| legal_UK = |
|
|
| legal_US = |
|
|
| legal_status = |
|
|
| routes_of_administration = ] |
|
|
| class = ] |
|
|
|
|
|
<!--Pharmacokinetic data--> |
|
|
| bioavailability = |
|
|
| protein_bound = |
|
|
| metabolism = |
|
|
| elimination_half-life = |
|
|
| excretion = |
|
|
|
|
|
<!-- Identifiers --> |
|
|
| CAS_number_Ref = {{cascite|correct|CAS}} |
|
|
| CAS_number = 182133-25-1 |
|
|
| CAS_supplemental = <br />182133-27-3 (]) |
|
|
| ATC_prefix = |
|
|
| ATC_suffix = |
|
|
| ATC_supplemental = |
|
|
| PubChem = 179337 |
|
|
| IUPHAR_ligand = |
|
|
| DrugBank_Ref = |
|
|
| DrugBank = |
|
|
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
|
|
| ChemSpiderID = 156104 |
|
| UNII_Ref = {{fdacite|correct|FDA}} |
|
| UNII_Ref = {{fdacite|correct|FDA}} |
|
| UNII = E569WG6E60 |
|
| UNII = E569WG6E60 |
|
|
| KEGG = D02993 |
|
| verifiedrevid = 443453020 |
|
|
|
| ChEBI = |
|
|ImageFile=Arzoxifene.svg |
|
|
|
| ChEMBL_Ref = {{ebicite|correct|EBI}} |
|
|ImageSize=180px |
|
|
|
| ChEMBL = 226267 |
|
|IUPACName=2-(4-Methoxyphenyl)-3--1-benzothiophen-6-ol |
|
|
|
| synonyms = LY-353381 |
|
|OtherNames= |
|
|
|
|
|
|Section1= {{Chembox Identifiers |
|
|
|
<!--Chemical data--> |
|
| CASNo_Ref = {{cascite|correct|??}} |
|
|
|
| C=28 | H=29 | N=1 | O=4 | S=1 |
|
| CASNo = <!-- blanked - oldvalue: 182133-25-1 --> |
|
|
|
| SMILES = COC1=CC=C(C=C1)C2=C(C3=C(S2)C=C(C=C3)O)OC4=CC=C(C=C4)OCCN5CCCCC5 |
|
| ChEMBL = 226267 |
|
|
|
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
|
| PubChem=179337 |
|
|
|
| StdInChI = 1S/C28H29NO4S/c1-31-22-8-5-20(6-9-22)28-27(25-14-7-21(30)19-26(25)34-28)33-24-12-10-23(11-13-24)32-18-17-29-15-3-2-4-16-29/h5-14,19,30H,2-4,15-18H2,1H3 |
|
| SMILES=COC1=CC=C(C=C1)C2=C(C3=C(S2) C=C(C=C3)O)OC4=CC=C(C=C4)OCCN5CCCCC5 |
|
|
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
|
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
|
| ChemSpiderID = 156104 |
|
|
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
|
|
| StdInChIKey = MCGDSOGUHLTADD-UHFFFAOYSA-N |
|
| StdInChIKey = MCGDSOGUHLTADD-UHFFFAOYSA-N |
|
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
|
|
| StdInChI=1S/C28H29NO4S/c1-31-22-8-5-20(6-9-22)28-27(25-14-7-21(30)19-26(25)34-28)33-24-12-10-23(11-13-24)32-18-17-29-15-3-2-4-16-29/h5-14,19,30H,2-4,15-18H2,1H3 |
|
|
}} |
|
|
|Section2= {{Chembox Properties |
|
|
| Formula=C<sub>28</sub>H<sub>29</sub>NO<sub>4</sub>S |
|
|
| MolarMass=475.60 g/mol |
|
|
| Appearance= |
|
|
| Density= |
|
|
| MeltingPt= |
|
|
| BoilingPt= |
|
|
| Solubility= |
|
|
}} |
|
|
|Section3= {{Chembox Hazards |
|
|
| MainHazards= |
|
|
| FlashPt= |
|
|
| Autoignition= |
|
|
}} |
|
|
}} |
|
}} |
|
|
|
|
|
'''Arzoxifene''' is a ].<ref name="pmid17654759">{{cite journal |author=Overk CR, Peng KW, Asghodom RT, ''et al.'' |title=Structure-activity relationships for a family of benzothiophene selective estrogen receptor modulators including raloxifene and arzoxifene |journal=ChemMedChem |volume=2 |issue=10 |pages=1520–6 |year=2007 |pmid=17654759 |doi=10.1002/cmdc.200700104}}</ref> It is a potent ] ] in mammary and uterine tissue while acting as an estrogen ] to maintain bone density and lower serum cholesterol. Arzoxifene is a highly effective agent for prevention of mammary cancer induced in the rat by the carcinogen ] and is significantly more potent than raloxifene in this regard. Arzoxifene is devoid of the uterotrophic effects of tamoxifen, suggesting that, in contrast to tamoxifen, it is unlikely that the clinical use of arzoxifene will increase the risk of developing endometrial carcinoma. |
|
'''Arzoxifene''' ({{abbrlink|INN|International Nonproprietary Name}}; developmental code name '''LY-353381''') is a ] (SERM) of the ] group which was never marketed.<ref name="pmid17654759">{{cite journal |vauthors=Overk CR, Peng KW, Asghodom RT |title=Structure-activity relationships for a family of benzothiophene selective estrogen receptor modulators including raloxifene and arzoxifene |journal=ChemMedChem |volume=2 |issue=10 |pages=1520–6 |year=2007 |pmid=17654759 |doi=10.1002/cmdc.200700104|s2cid=35664796 |display-authors=etal}}</ref> It is a potent ] ] in mammary and uterine tissue while acting as an estrogen ] to maintain bone density and lower serum cholesterol. Arzoxifene is a highly effective agent for prevention of mammary cancer induced in the rat by the ] ] and is significantly more potent than raloxifene in this regard. Arzoxifene is devoid of the uterotrophic effects of tamoxifen, suggesting that, in contrast to tamoxifen, it is unlikely that the clinical use of arzoxifene will increase the risk of developing endometrial carcinoma. |
|
|
|
|
|
|
==Pharmacology== |
|
== Clinical studies == |
|
|
|
Arzoxifene is a ] (SERM), and hence is a mixed ] and ] of the ] with ] ]ic and ]ic activity.<ref name="pmid25210448">{{cite journal | vauthors = Martinkovich S, Shah D, Planey SL, Arnott JA | title = Selective estrogen receptor modulators: tissue specificity and clinical utility | journal = Clin Interv Aging | volume = 9 | pages = 1437–52 | date = 2014 | pmid = 25210448 | pmc = 4154886 | doi = 10.2147/CIA.S66690 | doi-access = free }}</ref> It has antiestrogenic effects in the ], mixed estrogenic and antiestrogenic effects in the ], and estrogenic effects in ].<ref name="pmid25210448" /> The medication has been found to suppress ] levels in ] women, increase ] levels, and decrease ] and ] levels.<ref name="pmid25210448" /> |
|
|
|
|
|
|
==Research== |
|
In a phase 3 clinical study in postmenopausal women, arzoxifene was shown to increase bone spine and hip mineral density and had no effect on the uterus and endometrium.<ref name="pmid19351734">{{cite journal | author = Bolognese M, Krege JH, Utian WH, Feldman R, Broy S, Meats DL, Alam J, Lakshmanan M, Omizo M | title = Effects of arzoxifene on bone mineral density and endometrium in postmenopausal women with normal or low bone mass | journal = J. Clin. Endocrinol. Metab. | volume = 94 | issue = 7 | pages = 2284–9 | year = 2009 | month = July | pmid = 19351734 | doi = 10.1210/jc.2008-2143 | url = }}</ref> |
|
|
|
In a phase 3 clinical study in postmenopausal women, arzoxifene was shown to increase bone spine and hip mineral density and had no effect on the uterus and endometrium.<ref name="pmid19351734">{{cite journal | vauthors = Bolognese M, Krege JH, Utian WH, Feldman R, Broy S, Meats DL, Alam J, Lakshmanan M, Omizo M | title = Effects of arzoxifene on bone mineral density and endometrium in postmenopausal women with normal or low bone mass | journal = J. Clin. Endocrinol. Metab. | volume = 94 | issue = 7 | pages = 2284–9 |date=July 2009 | pmid = 19351734 | doi = 10.1210/jc.2008-2143 | doi-access = free }}</ref> |
|
|
|
|
|
Lilly announced in August 2009 that preliminary results from a five year clinical study showed that arzoxifene met its primary endpoints of reduction in vertebral fractures and breast cancer in postmenopausal women. However arzoxifene failed to meet secondary endpoints of reduction in non-vertebral fractures and cardiovascular events and improvements in cognitive function. Based on these results, Lilly announced they are discontinuing further development of the drug and would not seek regulatory approval.<ref name="Lilly_2009">{{cite web | author = | title = Lilly Reports on Outcome of Phase III Study of Arzoxifene | url = http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=403905 | archiveurl = | date = 2009-08-18 | work = Press Release | publisher = Eli Lilly and Company | accessdate = 2009-08-24}}</ref> |
|
Lilly announced in August 2009 that preliminary results from a five-year clinical study showed that arzoxifene met its primary endpoints of reduction in vertebral fractures and breast cancer in postmenopausal women. However arzoxifene failed to meet secondary endpoints of reduction in non-vertebral fractures and cardiovascular events and improvements in cognitive function. Based on these results, Lilly announced they are discontinuing further development of the drug and would not seek regulatory approval.<ref name="Lilly_2009">{{cite web | title = Lilly Reports on Outcome of Phase III Study of Arzoxifene | url = http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=403905 | date = 2009-08-18 | work = Press Release | publisher = Eli Lilly and Company | access-date = 2009-08-24}}</ref> |
|
|
|
|
|
|
A 2015 ] found that arzoxifene significantly reduced the risk of ] ({{abbrlink|RR|relative risk}} = 0.415) and to a greater extent than ] ({{abbr|RR|relative risk}} = 0.572) or ] ({{abbr|RR|relative risk}} = 0.708).<ref name="pmid26582062">{{cite journal | vauthors = Mocellin S, Pilati P, Briarava M, Nitti D | title = Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials | journal = J. Natl. Cancer Inst. | volume = 108 | issue = 2 | year = 2016 | pmid = 26582062 | doi = 10.1093/jnci/djv318 | doi-access = free }}</ref> |
|
==Chemistry== |
|
|
] |
|
|
|
|
|
{{Cite journal|doi=10.1021/jm970167b|title=Discovery and Synthesis of phenoxy]- 2-(4-hydroxyphenyl)]benzothiophene: A Novel, Highly Potent, Selective Estrogen Receptor Modulator|pmid=9154963|year=1997|last1=Palkowitz|first1=Alan D.|last2=Glasebrook|first2=Andrew L.|last3=Thrasher|first3=K. Jeff|last4=Hauser|first4=Kenneth L.|last5=Short|first5=Lorri L.|last6=Phillips|first6=D. Lynn|last7=Muehl|first7=Brian S.|last8=Sato|first8=Masahiko|last9=Shetler|first9=Pamela K.|journal=Journal of Medicinal Chemistry|volume=40|issue=10|pages=1407–16}} |
|
|
|
|
|
|
==References== |
|
==References== |
|
{{reflist}} |
|
{{Reflist|2}} |
|
|
|
|
|
|
==External links== |
|
] |
|
|
|
* |
|
] |
|
|
] |
|
|
] |
|
|
] |
|
|
|
|
|
|
|
{{Estrogen receptor modulators}} |
|
|
|
|
|
|
] |
|
{{pharm-stub}} |
|
|
|
] |
|
|
] |
|
|
] |
|
|
] |
|
|
] |
|
|
] |