11β-Chloromethylestradiol

{{Short description|Chemical compound}}

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| IUPAC_name = (8S,9R,11S,13S,14S,17S)-11-(chloromethyl)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol

| image = 11β-Chloromethylestradiol.svg

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| class = Estrogen

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| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 71794-60-0

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = BRP4DW4SEE

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| PubChem = 67088

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| ChemSpiderID = 60438

| KEGG = C14307

| ChEBI = 34142

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| synonyms = 11β-CME2; CME; ORG-4333; 11β-(Chloromethyl)estra-1,3,5(10)-trien-3,17β-diol

| C=19 | H=25 | Cl=1 | O=2

| SMILES = C[C@]12C[C@@H]([C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=C3C=CC(=C4)O)CCl

| StdInChI_Ref =

| StdInChI = 1S/C19H25ClO2/c1-19-9-12(10-20)18-14-5-3-13(21)8-11(14)2-4-15(18)16(19)6-7-17(19)22/h3,5,8,12,15-18,21-22H,2,4,6-7,9-10H2,1H3/t12-,15+,16+,17+,18-,19+/m1/s1

| StdInChIKey_Ref =

| StdInChIKey = CADGCTOWBAPSFQ-OQFXVXKWSA-N

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11β-Chloromethylestradiol (11β-CME2; developmental code name ORG-4333) is a synthetic steroidal estrogen which was never marketed.{{cite journal | vauthors = Sasson S | title = Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor | journal = Pathologie-Biologie | volume = 39 | issue = 1 | pages = 59–69 | date = January 1991 | pmid = 2011412 }}{{cite journal | vauthors = Bindal RD, Carlson KE, Reiner GC, Katzenellenbogen JA | title = 11 beta-chloromethyl-[3H]estradiol-17 beta: a very high affinity, reversible ligand for the estrogen receptor | journal = Journal of Steroid Biochemistry | volume = 28 | issue = 4 | pages = 361–370 | date = October 1987 | pmid = 3669657 | doi = 10.1016/0022-4731(87)91052-1 }}{{cite journal | vauthors = Ratajczak T, Atrache V, Antes P, Comber M, Hähnel R | title = A comparison of 11 beta-chloromethylestradiol and tamoxifen aziridine as affinity labeling reagents for estrogen receptors | journal = Steroids | volume = 51 | issue = 5–6 | pages = 499–518 | date = 1988 | pmid = 3242173 | doi = 10.1016/0039-128x(88)90047-5 | s2cid = 11598932 }}{{cite journal | vauthors = Ratajczak T, Sheppard PN, Capon RJ, Hähnel R | title = The synthesis and study of some potential affinity labeling reagents for estrogen receptors | journal = Steroids | volume = 38 | issue = 5 | pages = 537–555 | date = November 1981 | pmid = 7324085 | doi = 10.1016/0039-128x(81)90053-2 | s2cid = 37503105 }}{{cite journal | vauthors = Reiner GC, Katzenellenbogen BS, Bindal RD, Katzenellenbogen JA | title = Biological activity and receptor binding of a strongly interacting estrogen in human breast cancer cells | journal = Cancer Research | volume = 44 | issue = 6 | pages = 2302–2308 | date = June 1984 | pmid = 6547074 | url = https://cancerres.aacrjournals.org/content/44/6/2302.short }}{{cite journal | vauthors = Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO | title = The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants | journal = Environmental Health Perspectives | volume = 103 | issue = Suppl 7 | pages = 113–122 | date = October 1995 | pmid = 8593856 | pmc = 1518887 | doi = 10.1289/ehp.95103s7113 }} It has very high affinity for the estrogen receptor and dissociates from it relatively slowly.{{cite journal | vauthors = Sasson S, Katzenellenbogen JA | title = Reversible, positive cooperative interaction of 11 beta-chloromethyl-[3H]estradiol-17 beta with the calf uterine estrogen receptor | journal = Journal of Steroid Biochemistry | volume = 33 | issue = 5 | pages = 859–865 | date = November 1989 | pmid = 2601330 | doi = 10.1016/0022-4731(89)90233-1 }}{{cite journal| vauthors = Katzenellenbogen JA, Muthyala R |title=Interactions of exogenous endocrine active substances with nuclear receptors|journal=Pure and Applied Chemistry|volume=75|issue=11–12|year=2003|pages=1797–1817|issn=1365-3075|doi=10.1351/pac200375111797|s2cid=86680540|doi-access=free}} It was originally thought that 11β-CME2 might be a covalent ligand of the estrogen receptors, but its binding was subsequently shown to be fully reversible. The relative binding affinity of 11β-CME2 for the estrogen receptors ranges from 230 to 3,320% of that of estradiol depending on the study.{{cite journal | vauthors = Fink BE, Mortensen DS, Stauffer SR, Aron ZD, Katzenellenbogen JA | title = Novel structural templates for estrogen-receptor ligands and prospects for combinatorial synthesis of estrogens | journal = Chemistry & Biology | volume = 6 | issue = 4 | pages = 205–219 | date = April 1999 | pmid = 10099132 | doi = 10.1016/S1074-5521(99)80037-4 | doi-access = free }}{{cite journal | vauthors = Sasson S, Katzenellenbogen JA | title = Reversible, positive cooperative interaction of 11 beta-chloromethyl-[3H]estradiol-17 beta with the calf uterine estrogen receptor | journal = Journal of Steroid Biochemistry | volume = 33 | issue = 5 | pages = 859–865 | date = November 1989 | pmid = 2601330 | doi = 10.1016/0022-4731(89)90233-1 }}{{cite journal | vauthors = Wolohan P, Reichert DE | title = CoMSIA and docking study of rhenium based estrogen receptor ligand analogs | journal = Steroids | volume = 72 | issue = 3 | pages = 247–260 | date = March 2007 | pmid = 17280694 | pmc = 1964785 | doi = 10.1016/j.steroids.2006.11.011 }}{{cite journal | vauthors = Quivy J, Leclercq G, Deblaton M, Henrot P, Velings N, Norberg B, Evrard G, Zeicher M | display-authors = 6 | title = Synthesis, structure and biological properties of Z-17alpha-(2-iodovinyl)-11beta-chloromethyl estradiol-17beta (Z-CMIV), a high affinity ligand for the characterization of estrogen receptor-positive tumors | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 59 | issue = 1 | pages = 103–117 | date = September 1996 | pmid = 9009243 | doi = 10.1016/s0960-0760(96)00007-6 | s2cid = 54359888 }} 11β-CME2 also has about 14% of the relative binding affinity of estradiol for sex hormone-binding globulin (SHBG). The compound has been developed as a radiolabel for the ERs.