2-Methoxyestradiol disulfamate

Chemical compound [(8R,9S,13S,14S,17S)-2-methoxy-13-methyl-3-sulfamoyloxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] sulfamate STX-140.svg skin-invert-image correct CAS 401600-86-0 correct FDA S57SQE6LE5 9804302 DB08416 7980062 218382 2-Methoxyestradiol disulfamate; 2-Methoxyestradiol 3,17β-disulfamate; 2-Methoxyestradiol-3,17β-O,O-bis(sulfamate); 3,17β-bis-Sulfamoyloxy-2-methoxyestra-1,3,5(10)-triene 19 28 2 7 2 C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2OS(=O)(=O)N)CCC4=CC(=C(C=C34)OC)OS(=O)(=O)N 1S/C19H28N2O7S2/c1-19-8-7-12-13(15(19)5-6-18(19)28-30(21,24)25)4-3-11-9-17(27-29(20,22)23)16(26-2)10-14(11)12/h9-10,12-13,15,18H,3-8H2,1-2H3,(H2,20,22,23)(H2,21,24,25)/t12-,13+,15-,18-,19-/m0/s1 AQSNIXKAKUZPSI-SSTWWWIQSA-N 2-Methoxyestradiol disulfamate (developmental code STX-140; also known as 2-methoxyestradiol 3,17β-O,O-bis(sulfamate)) is a synthetic, oral active anti-cancer medication which was previously under development for potential clinical use. Leese MP, Leblond B, Smith A, Newman SP, Di Fiore A, De Simone G, Supuran CT, Purohit A, Reed MJ, Potter BV 6 2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: synthesis, in vitro SAR, protein crystallography, and in vivo activity Journal of Medicinal Chemistry 49 26 7683–7696 December 2006 17181151 10.1021/jm060705x Thomas MP, Potter BV Estrogen O-sulfamates and their analogues: Clinical steroid sulfatase inhibitors with broad potential The Journal of Steroid Biochemistry and Molecular Biology 153 19 160–169 September 2015 25843211 10.1016/j.jsbmb.2015.03.012 24116740 It has improved potency, low metabolism, and good pharmacokinetic properties relative to 2-methoxyestradiol (2-MeO-E2). Thomas MP, Potter BV Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women's Health Journal of Medicinal Chemistry 58 19 7634–7658 October 2015 25992880 5159624 10.1021/acs.jmedchem.5b00386 It is also a potent inhibitor of steroid sulfatase, the enzyme that catalyzes the desulfation of steroids such as estrone sulfate and dehydroepiandrosterone sulfate (DHEA-S). 2-Methoxyestradiol disulfamate exhibits anti-angiogenic activity and induction of cell cycle arrest and apoptosis in human tumor xenografts, with clinical potential for hormone–independent tumors. Some of this activity stems from tubulin binding at the colchicine site and disruption of interphase microtubules. 2-Methoxyestradiol disulfamate is highly active in tumors that are resistant to chemotherapy. Newman SP, Foster PA, Stengel C, Day JM, Ho YT, Judde JG, Lassalle M, Prevost G, Leese MP, Potter BV, Reed MJ, Purohit A 6 STX140 is efficacious in vitro and in vivo in taxane-resistant breast carcinoma cells Clinical Cancer Research 14 2 597–606 January 2008 18223236 10.1158/1078-0432.CCR-07-1717 free In xenograft models of breast and prostate cancer complete cures were achieved after oral treatment with 2-methoxyestradiol disulfamate and drug-resistant tumors also shrank in size after oral treatment. Conventional treatments for hormone-independent cancers targeting tubulin are associated with side effects, such as neurotoxicity, and can only be given infrequently and intravenously. 2-Methoxyestradiol disulfamate is more effective on the same tumors, blocks metastatic spread without the peripheral neuropathy associated with current clinical anticancer drugs. Meyer-Losic F, Newman SP, Day JM, Reed MJ, Kasprzyk PG, Purohit A, Foster PA STX140, but not paclitaxel, inhibits mammary tumour initiation and progression in C3(1)/SV40 T/t-antigen transgenic mice PLOS ONE 8 12 e80305 2013-12-06 24324595 3855596 10.1371/journal.pone.0080305 2013PLoSO...880305M free Tan M See also Steroid sulfatase § Inhibitors References Category:Abandoned drugs Category:Angiogenesis inhibitors Category:Antineoplastic drugs Category:Estranes Category:Methoxy compounds Category:Human metabolites Category:Microtubule inhibitors Category:Steroid sulfatase inhibitors Category:Sulfamate esters