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Bis-choline tetrathiomolybdate, or WTX101, is a salt of tetrathiomolybdate (TTM, MoS42−) and choline currently under investigation as a therapy against Wilson's disease, a rare and potentially fatal disease in which the body cannot regulate copper. Wilson disease is an autosomal recessive genetic disorder that is manifested by serious hepatic, neurologic or psychiatric symptoms. The disease is fatal if left undiagnosed and untreated. It is estimated that approximately 1 individual in every 15,000 worldwide have Wilson's disease, corresponding to approximately 30,000 individuals in the European Union and approximately 20,000 in the United States.〔Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML, 2007. "Wilson's disease". ''Lancet'' 369: 397-408.〕 Bis-choline tetrathiomolybdate has been evaluated in clinical trials in patients with various forms of cancer〔Berenson JR, Boccia RV, Bashey A, Levine AM, Koc ON, Callahan JA, Mazar AP, Reich SD, 2006. "Phase I Study of the (Zn ) Superoxide Dismutase (SOD1) Inhibitor ATN-224 (Bis-Choline Tetrathiomolybdate) in Patients with Advanced Hematologic Malignancies". Presentation at the Amer Soc Hematol 2006 Annual Meeting, ''Blood'' 108: Abstract 2593.〕〔Lin J, Zahurak M, Beer TM, Ryan CJ, Wilding G, Mathew P, Morris M, Callahan JA, Gordon G, Reich SD, Carducci MA, Antonarakis ES, 2011. "A non-comparative randomized phase II study of 2 doses of ATN-224, a copper/zinc superoxide dismutase inhibitor, in patients with biochemically recurrent hormone-naive prostate cancer". ''Urologic oncology''.〕〔Lowndes SA, Adams A, Timms A, Fisher N, Smythe J, Watt SM, Joel S, Donate F, Hayward C, Reich S, Middleton M, Mazar A, Harris AL, 2008. "Phase I study of copper-binding agent ATN-224 in patients with advanced solid tumors". ''Clin Cancer Res'' 14: 7526-7534.〕 and has received orphan designation in the US and EU as a potential therapy against Wilson disease.〔(Public summary of opinion on orphan designation: Choline tetrathiomolybdate for the treatment of Wilson's disease ), EMA/COMP/795268/2012, ATN-224, 18 February 2013.〕〔(Orphan Drug Designations and Approvals: choline tetrathiomolybdate ), U.S. Food and Drug Administration, 25 August 2011〕 Bis-choline salt of tetrathiomolybdate is a de-coppering therapy in clinical development against Wilson disease under the code name WTX101 by Wilson Therapeutics AB. Wilson Therapeutics was founded by HealthCap in 2012. == Mechanism of action == Tetrathiomolybdate has a unique mechanism of action through which it selectively forms highly stable complexes with copper and proteins. These complexes are then believed to be primarily excreted via the bile, restoring the normal excretion route of copper that is impaired in patients with Wilson disease.〔Komatsu Y, Sadakata I, Ogra Y, Suzuki KT, 2000. "Excretion of copper complexed with thiomolybdate into the bile and blood in LEC rats". ''Chem Biol Interact'' 124: 217-231.〕〔McQuaid A, Mason J, 1991. "A comparison of the effects of penicillamine, trientine, and trithiomolybdate on ()-labeled metallothionein in vitro; implications for Wilson's disease therapy". ' 41: 87-92.〕〔Ogra Y, Ohmichi M, Suzuki KT, 1995. "Systemic dispositions of molybdenum and copper after tetrathiomolybdate injection in LEC rats". ''Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements'' 9: 165-169.〕 The binding and excretion mechanism of WTX101 is stable; whereas many de-coppering agents form unstable complexes that are excreted via urine.〔Riha M, Karlickova J, Filipsky T, Macakova K, Hrdina R, Mladenka P, 2013. "Novel method for rapid copper chelation assessment confirmed low affinity of D-penicillamine for copper in comparison with trientine and 8-hydroxyquinolines". ' 123: 80-87.〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Bis-choline tetrathiomolybdate」の詳細全文を読む スポンサード リンク
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