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1. 发明申请

WO2007053747A2 MODULATING ENDOPLASMIC RETICULUM STRESS IN THE TREATMENT OF TUBEROUS SCLEROSIS 审中-公开
标题翻译：调节内质网应激治疗结石性硬结症
公开(公告)号：WO2007053747A2
公开(公告)日：2007-05-10
申请号：PCT/US2006/042802
申请日：2006-11-01
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , HOTAMISLIGIL, Gokhan, S. , OZCAN, Umut , MANNING, Brendan, D.
发明人： HOTAMISLIGIL, Gokhan, S. , OZCAN, Umut , MANNING, Brendan, D.
IPC分类号： A61K31/397
CPC分类号： A61K31/343 , A61K31/192 , A61K31/397 , A61K31/706 , A61K45/06 , G01N33/6893
摘要： Endoplasmic reticulum stress has been found to be associated with the genetic disease tuberous sclerosis. Tuberous sclerosis is cause by defects in the two genes, TSC1 and TSC2. Agents that modulate ER stress may be used to treat tuberous sclerosis and other hamartomatous diseases. In particular, 4-phenyl butyric acid (PBA) has been shown to reduce ER stress is TSC-deficient cells. Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide arid glycerol may also be useful in treating tuberous sclerosis. The present invention provides methods of treating a subject suffering from tuberous sclerosis using ER stress reducers such as PBA, TUDCA, UDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in TSC-deficient cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating tuberous sclerosis.
摘要翻译：已发现内质网应激与遗传性疾病结节性硬化有关。 TSC1和TSC2这两个基因的缺陷导致了结节性硬化。调节内质网应激的药物可用于治疗结节性硬化症和其他血管病性疾病。特别地，已显示4-苯基丁酸（PBA）减少ER应激是TSC缺陷型细胞。用于降低ER应激的其它化合物是化学伴侣分子如三甲胺N-氧化物和甘油，也可用于治疗结节性硬化。本发明提供了使用ER应激减少剂例如PBA，TUDCA，UDCA和TMAO治疗患有结节性硬化症的受试者的方法。还提供了通过鉴定降低TSC缺陷细胞中ER应激标志物水平的试剂来筛选ER应激减少剂的方法。这些药物可用于治疗结节性硬化症的方法和药物组合物中。

2. 发明申请

WO2006020755A9 METHODS FOR IDENTIFYING INHIBITORS OF THE MTOR PATHWAY AS DIABETES THERAPEUTICS 审中-公开
标题翻译：用于鉴定作为糖尿病治疗剂的MTOR途径的抑制剂的方法
公开(公告)号：WO2006020755A9
公开(公告)日：2006-03-23
申请号：PCT/US2005028523
申请日：2005-08-10
申请人： BETH ISRAEL HOSPITAL , CANTLEY LEWIS C , SHAW REUBEN J , MANNING BRENDAN D
发明人： CANTLEY LEWIS C , SHAW REUBEN J , MANNING BRENDAN D
IPC分类号： C12Q1/48 , A61K31/00 , G01N33/68
CPC分类号： G01N33/6893 , C12Q1/485 , G01N2800/042
摘要： The invention relates to inhibition of mTOR, p70S6K1 or Rheb kinase activity for treating disorders including diabetes. The invention also relates to screening for agents that inhibit the activities of mTOR, p70S6K1 or Rheb proteins, which are useful in the treatment of diabetes, as well as preparing compounds for treatment of diabetes.
摘要翻译：本发明涉及抑制mTOR，p70S6K1或Rheb激酶活性来治疗包括糖尿病在内的疾病。本发明还涉及抑制可用于治疗糖尿病的mTOR，p70S6K1或Rheb蛋白的活性的药剂的筛选，以及制备用于治疗糖尿病的化合物。

3. 发明申请

WO2006020755A2 METHODS FOR IDENTIFYING DIABETES THERAPEUTICS 审中-公开
标题翻译：鉴定糖尿病治疗方法
公开(公告)号：WO2006020755A2
公开(公告)日：2006-02-23
申请号：PCT/US2005/028523
申请日：2005-08-10
申请人： BETH ISRAEL DEACONESS MEDICAL CENTER, INC. , CANTLEY, Lewis, C. , SHAW, Reuben, J. , MANNING, Brendan, D.
发明人： CANTLEY, Lewis, C. , SHAW, Reuben, J. , MANNING, Brendan, D.
IPC分类号： C12Q1/48 , G01N33/68 , A61K31/00
CPC分类号： G01N33/6893 , C12Q1/485 , G01N2800/042
摘要： The invention relates to inhibition of mTOR, p70S6K1 or Rheb kinase activity for treating disorders including diabetes. The invention also relates to screening for agents that inhibit the activities of mTOR, p70S6K1 or Rheb proteins, which are useful in the treatment of diabetes, as well as preparing compounds for treatment of diabetes.
摘要翻译：本发明涉及抑制mTOR，p70S6K1或Rheb激酶活性来治疗包括糖尿病在内的疾病。本发明还涉及抑制可用于治疗糖尿病的mTOR，p70S6K1或Rheb蛋白的活性的药剂的筛选，以及制备用于治疗糖尿病的化合物。

4. 发明申请

WO2007053747A3 MODULATING ENDOPLASMIC RETICULUM STRESS IN THE TREATMENT OF TUBEROUS SCLEROSIS 审中-公开
标题翻译：治疗管状性溃疡的内源性内皮应激调节
公开(公告)号：WO2007053747A3
公开(公告)日：2007-10-25
申请号：PCT/US2006042802
申请日：2006-11-01
申请人： HARVARD COLLEGE , HOTAMISLIGIL GOKHAN S , OZCAN UMUT , MANNING BRENDAN D
发明人： HOTAMISLIGIL GOKHAN S , OZCAN UMUT , MANNING BRENDAN D
IPC分类号： A61K31/00
CPC分类号： A61K31/343 , A61K31/192 , A61K31/397 , A61K31/706 , A61K45/06 , G01N33/6893
摘要： Endoplasmic reticulum stress has been found to be associated with the genetic disease tuberous sclerosis. Tuberous sclerosis is cause by defects in the two genes, TSC1 and TSC2. Agents that modulate ER stress may be used to treat tuberous sclerosis and other hamartomatous diseases. In particular, 4-phenyl butyric acid (PBA) has been shown to reduce ER stress is TSC-deficient cells. Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide arid glycerol may also be useful in treating tuberous sclerosis. The present invention provides methods of treating a subject suffering from tuberous sclerosis using ER stress reducers such as PBA, TUDCA, UDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in TSC-deficient cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating tuberous sclerosis.
摘要翻译：已经发现内质网应激与遗传性疾病结节性硬化有关。结节性硬化是两种基因TSC1和TSC2的缺陷引起的。调节ER应激的药物可用于治疗结节性硬化症和其他错构瘤疾病。特别地，已经显示4-苯基丁酸（PBA）减少ER应激是TSC缺陷型细胞。可用于减少ER应激的其他化合物是化学伴侣如三甲胺N-氧化物和甘油也可用于治疗结节性硬化症。本发明提供使用ER减压剂如PBA，TUDCA，UDCA和TMAO治疗患有结节性硬化症的受试者的方法。还提供了通过鉴定减少TSC缺陷细胞中ER应激标记物水平的试剂筛选ER应力减少剂的方法。这些试剂可用于治疗结节性硬化症的方法和药物组合物中。

5. 发明申请

WO2006020755A3 Methods for identifiying inhibitors of the MTOR pathway as diabetes therapeutics 审中-公开
标题翻译：鉴定MTOR途径抑制剂作为糖尿病治疗剂的方法
公开(公告)号：WO2006020755A3
公开(公告)日：2006-07-06
申请号：PCT/US2005028523
申请日：2005-08-10
申请人： BETH ISRAEL HOSPITAL , CANTLEY LEWIS C , SHAW REUBEN J , MANNING BRENDAN D
发明人： CANTLEY LEWIS C , SHAW REUBEN J , MANNING BRENDAN D
IPC分类号： C12Q1/48 , A61K31/00 , G01N33/68
CPC分类号： G01N33/6893 , C12Q1/485 , G01N2800/042
摘要： The invention relates to inhibition of mTOR, p70S6K1 or Rheb kinase activity for treating disorders including diabetes. The invention also relates to screening for agents that inhibit the activities of mTOR, p70S6K1 or Rheb proteins, which are useful in the treatment of diabetes, as well as preparing compounds for treatment of diabetes.
摘要翻译：本发明涉及抑制mTOR，p70S6K1或Rheb激酶活性来治疗包括糖尿病在内的疾病。本发明还涉及抑制可用于治疗糖尿病的mTOR，p70S6K1或Rheb蛋白的活性的药剂的筛选，以及制备用于治疗糖尿病的化合物。

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