发明名称 |
COMPOUNDS AND METHODS FOR ACEMIF INHIBITION AND THE TREATMENT OF PARASITES |
摘要 |
The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new pharmacophores, Hookworms are blood-feeding, intestinal nematode parasites infect up to 600 million people worldwide. Vaccination with recombinant Ancylostoma ceylanicum macrophage migration inhibitory factor (rAceMIF) provided partial protection from disease, thus establishing a "proof-of-concept" for targeting AceMIF to prevent or treat infection. A high-throughput screen (HTS) against rAceMIF identified six AceMIF-specific inhibitors. A non-steroidal anti-inflammatory drug (NSAID), sodium meclofenamate, could be tested in an animal model to assess the therapeutic efficacy in treating hookworm disease. Furosemide, an FDA-approved diuretic, exhibited submicromolar inhibition of rAceMIF tautomerase activity. Structure-activity relationships of a pharmacophore based on furosemide included one analogue that binds similarly to the active site, yet does not inhibit the Na-K-Cl symporter (NKCC1) responsible for diuretic activity. Compounds and methods for inhibiting AceMIF and treating parasitic, including hookworm infections represent additional aspects of the invention. |
申请公布号 |
WO2012033878(A2) |
申请公布日期 |
2012.03.15 |
申请号 |
WO2011US50767 |
申请日期 |
2011.09.08 |
申请人 |
YALE UNIVERSITY;LOLIS, ELIAS;CHO, YOONSANG;BUCALA, RICHARD;CAPPELLO, MICHAEL;VERMEIRE, JON, J. |
发明人 |
LOLIS, ELIAS;CHO, YOONSANG;BUCALA, RICHARD;CAPPELLO, MICHAEL;VERMEIRE, JON, J. |
分类号 |
A61K31/19;A61K31/045;A61K31/185;A61K31/195;A61K31/496;A61P33/00 |
主分类号 |
A61K31/19 |
代理机构 |
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代理人 |
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地址 |
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