11β-Chloromethylestradiol explained

11β-Chloromethylestradiol (11β-CME2; developmental code name ORG-4333) is a synthetic steroidal estrogen which was never marketed.^{[1] [2] [3] [4] [5] [6]} It has very high affinity for the estrogen receptor and dissociates from it relatively slowly.^{[7] [8]} 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.^{[9] [10] [11] [12]} 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.

See also

• 11β-Methoxyestradiol
• Moxestrol

Notes and References

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2. Bindal RD, Carlson KE, Reiner GC, Katzenellenbogen JA . 11 beta-chloromethyl-[3H]estradiol-17 beta: a very high affinity, reversible ligand for the estrogen receptor . Journal of Steroid Biochemistry . 28 . 4 . 361–370 . October 1987 . 3669657 . 10.1016/0022-4731(87)91052-1 .
3. Ratajczak T, Atrache V, Antes P, Comber M, Hähnel R . A comparison of 11 beta-chloromethylestradiol and tamoxifen aziridine as affinity labeling reagents for estrogen receptors . Steroids . 51 . 5–6 . 499–518 . 1988 . 3242173 . 10.1016/0039-128x(88)90047-5 . 11598932 .
4. Ratajczak T, Sheppard PN, Capon RJ, Hähnel R . The synthesis and study of some potential affinity labeling reagents for estrogen receptors . Steroids . 38 . 5 . 537–555 . November 1981 . 7324085 . 10.1016/0039-128x(81)90053-2 . 37503105 .
5. Reiner GC, Katzenellenbogen BS, Bindal RD, Katzenellenbogen JA . Biological activity and receptor binding of a strongly interacting estrogen in human breast cancer cells . Cancer Research . 44 . 6 . 2302–2308 . June 1984 . 6547074 .
6. Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO . The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants . Environmental Health Perspectives . 103 . Suppl 7 . 113–122 . October 1995 . 8593856 . 1518887 . 10.1289/ehp.95103s7113 .
7. Sasson S, Katzenellenbogen JA . Reversible, positive cooperative interaction of 11 beta-chloromethyl-[3H]estradiol-17 beta with the calf uterine estrogen receptor . Journal of Steroid Biochemistry . 33 . 5 . 859–865 . November 1989 . 2601330 . 10.1016/0022-4731(89)90233-1 .
8. Katzenellenbogen JA, Muthyala R . Interactions of exogenous endocrine active substances with nuclear receptors. Pure and Applied Chemistry. 75. 11–12. 2003. 1797–1817. 1365-3075. 10.1351/pac200375111797. 86680540. free.
9. Fink BE, Mortensen DS, Stauffer SR, Aron ZD, Katzenellenbogen JA . Novel structural templates for estrogen-receptor ligands and prospects for combinatorial synthesis of estrogens . Chemistry & Biology . 6 . 4 . 205–219 . April 1999 . 10099132 . 10.1016/S1074-5521(99)80037-4 . free .
10. Sasson S, Katzenellenbogen JA . Reversible, positive cooperative interaction of 11 beta-chloromethyl-[3H]estradiol-17 beta with the calf uterine estrogen receptor . Journal of Steroid Biochemistry . 33 . 5 . 859–865 . November 1989 . 2601330 . 10.1016/0022-4731(89)90233-1 .
11. Wolohan P, Reichert DE . CoMSIA and docking study of rhenium based estrogen receptor ligand analogs . Steroids . 72 . 3 . 247–260 . March 2007 . 17280694 . 1964785 . 10.1016/j.steroids.2006.11.011 .
12. Quivy J, Leclercq G, Deblaton M, Henrot P, Velings N, Norberg B, Evrard G, Zeicher M . 6 . 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 . The Journal of Steroid Biochemistry and Molecular Biology . 59 . 1 . 103–117 . September 1996 . 9009243 . 10.1016/s0960-0760(96)00007-6 . 54359888 .