公开(公告)号：US20180071279A1

公开(公告)日：2018-03-15

申请号：US15815426

申请日：2017-11-16

申请人： The General Hospital Corporation

发明人： Vamsi K. Mootha ,  Vishal Gohil ,  Sunil Sheth ,  Yuhua Ji

IPC分类号： A61K31/495 ,  A61K45/06 ,  G01N33/50 ,  A61K31/382 ,  A61K31/55 ,  A61K31/5415 ,  A61K31/496

CPC分类号： A61K31/495 ,  A61K31/382 ,  A61K31/496 ,  A61K31/5415 ,  A61K31/55 ,  A61K45/06 ,  C12Y207/07014 ,  G01N33/502 ,  G01N2333/9125 ,  Y02A50/411 ,  Y02A50/414

摘要： Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

公开(公告)号：US20160324850A1

公开(公告)日：2016-11-10

申请号：US15216876

申请日：2016-07-22

申请人： The General Hospital Corporation

发明人： Vamsi K. Mootha ,  Vishal Gohil ,  Sunil Sheth ,  Yuhua Ji

IPC分类号： A61K31/495 ,  G01N33/50

CPC分类号： A61K31/495 ,  A61K31/382 ,  A61K31/496 ,  A61K31/5415 ,  A61K31/55 ,  A61K45/06 ,  C12Y207/07014 ,  G01N33/502 ,  G01N2333/9125 ,  Y02A50/411 ,  Y02A50/414

摘要： Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

摘要翻译： 模型系统已经表明，将细胞从氧化磷酸化（OXPHOS）转变为糖酵解的依赖可以防止细胞死亡。 然而，利用这一策略的治疗潜力，由于缺乏重建能量代谢的临床安全药物而受到限制。 本发明鉴定能够调节氧化代谢的无毒小分子（例如药物样化合物）。 一种鉴定的化合物包括麦地利。 如本文所述，meclizine及其对映体S-meclizine将OXPHOS重定向至糖酵解。 这些化合物可以是退行性疾病如糖尿病，亨廷顿顿氏病，帕金森病和阿尔茨海默氏病和/或缺血性疾病中的保护性或治疗性的，包括但不限于中风，心脏病发作或再灌注损伤。

公开(公告)号：US09399032B2

公开(公告)日：2016-07-26

申请号：US13320348

申请日：2010-05-14

申请人： Vamsi K. Mootha ,  Vishal Gohil ,  Sunil Sheth ,  Yuhua Ji

发明人： Vamsi K. Mootha ,  Vishal Gohil ,  Sunil Sheth ,  Yuhua Ji

IPC分类号： A61K31/495 ,  A61P9/10 ,  A61K31/382 ,  A61K31/496 ,  A61K31/5415 ,  A61K31/55

CPC分类号： A61K31/495 ,  A61K31/382 ,  A61K31/496 ,  A61K31/5415 ,  A61K31/55 ,  A61K45/06 ,  C12Y207/07014 ,  G01N33/502 ,  G01N2333/9125 ,  Y02A50/411 ,  Y02A50/414

摘要： Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

摘要翻译： 模型系统已经表明，将细胞从氧化磷酸化（OXPHOS）转变为糖酵解的依赖可以防止细胞死亡。 然而，利用这一策略的治疗潜力，由于缺乏重建能量代谢的临床安全药物而受到限制。 本发明鉴定能够调节氧化代谢的无毒小分子（例如药物样化合物）。 一种鉴定的化合物包括麦地利。 如本文所述，meclizine及其对映体S-meclizine将OXPHOS重定向至糖酵解。 这些化合物可以是退行性疾病如糖尿病，亨廷顿顿氏病，帕金森病和阿尔茨海默氏病和/或缺血性疾病中的保护性或治疗性的，包括但不限于中风，心脏病发作或再灌注损伤。

公开(公告)号：US20120136007A1

公开(公告)日：2012-05-31

申请号：US13320348

申请日：2010-05-14

申请人： Vamsi K. Mootha ,  Vishal Gohil ,  Sunil Sheth ,  Yuhua Ji

发明人： Vamsi K. Mootha ,  Vishal Gohil ,  Sunil Sheth ,  Yuhua Ji

IPC分类号： A61K31/495 ,  C12Q1/48 ,  A61P9/10 ,  A61P33/06 ,  A61P25/16 ,  A61P13/12 ,  A61P33/00 ,  A61P33/02 ,  G01N33/53 ,  A61P25/28

CPC分类号： A61K31/495 ,  A61K31/382 ,  A61K31/496 ,  A61K31/5415 ,  A61K31/55 ,  A61K45/06 ,  C12Y207/07014 ,  G01N33/502 ,  G01N2333/9125 ,  Y02A50/411 ,  Y02A50/414

摘要： Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

摘要翻译： 模型系统已经表明，将细胞从氧化磷酸化（OXPHOS）转变为糖酵解的依赖可以防止细胞死亡。 然而，利用这一策略的治疗潜力，由于缺乏重建能量代谢的临床安全药物而受到限制。 本发明鉴定能够调节氧化代谢的无毒小分子（例如药物样化合物）。 一种鉴定的化合物包括麦地利。 如本文所述，meclizine及其对映体S-meclizine将OXPHOS重定向至糖酵解。 这些化合物可以是退行性疾病如糖尿病，亨廷顿顿氏病，帕金森病和阿尔茨海默氏病和/或缺血性疾病中的保护性或治疗性的，包括但不限于中风，心脏病发作或再灌注损伤。