公开(公告)号：US20050036992A1

公开(公告)日：2005-02-17

申请号：US10745334

申请日：2003-12-22

申请人： Enrique Saez ,  Peter Tontonoz ,  Bryan Laffitte ,  Jing Li

发明人： Enrique Saez ,  Peter Tontonoz ,  Bryan Laffitte ,  Jing Li

IPC分类号： A01N41/06 ,  A61K20060101 ,  A61K48/00 ,  C12N5/08 ,  C12N15/85 ,  C12Q1/68 ,  G01N33/53 ,  G01N33/566

CPC分类号： C12Q1/6897 ,  G01N33/566

摘要： This invention provides novel methods for modulating expression of glut4 and other genes involved in glucose metabolism, and methods for treating or ameliorating diabetes and related diseases. The methods comprise administering to cells in a subject an effective amount of an LXR agonist and thereby modulating expression of those genes that are important for glucose uptake or gluconeogenesis. The modulation will lead to increased uptake of glucose by cells in the subject and/or reduced glucose output in the liver, and accordingly ameliorate symptoms associated with, e.g., type II diabetes.

摘要翻译： 本发明提供调节葡萄糖代谢过程中glut4等基因表达的新方法，以及治疗或改善糖尿病及相关疾病的方法。 所述方法包括向受试者的细胞施用有效量的LXR激动剂，从而调节对葡萄糖摄取或糖异生重要的那些基因的表达。 调节将导致受试者中细胞对葡萄糖的摄取增加和/或肝脏中葡萄糖产量降低，从而改善与例如II型糖尿病相关的症状。

公开(公告)号：US06586455B1

公开(公告)日：2003-07-01

申请号：US09331534

申请日：2000-02-01

申请人： Ronald M. Evans ,  Peter Tontonoz ,  Bruce M. Spiegelman ,  Barry M. Forman

发明人： Ronald M. Evans ,  Peter Tontonoz ,  Bruce M. Spiegelman ,  Barry M. Forman

IPC分类号： A61K314406

CPC分类号： A61K45/06 ,  A61K31/426 ,  A61K31/4406 ,  A61K2300/00

摘要： In accordance with the present invention, it has been discovered that PPAR&ggr; is expressed consistently in each of the major histologic types of human liposarcoma. It has further been discovered that maximal activation of PPAR&ggr; with exogenous ligand (a thiazolidinedione or derivative thereof) promotes terminal differentiation of primary human liposarcoma cells. It has still further been discovered that RXR-specific ligands are also potent adipogenic agents in cells expressing the PPAR&ggr;/RXR&agr; heterodimer, and that simultaneous treatment of liposarcoma cells with a thiazolidinedionyl moiety (a PPAR&ggr;-selective class of compounds) and an RXR-specific ligand results in an additive stimulation of differentiation. Accordingly, according to the invention, there have been identified compositions which are useful for the treatment of liposarcomas.

摘要翻译： 根据本发明，已经发现PPARγ在人脂肪肉瘤的主要组织学类型中均一致地表达。 进一步发现，外源配体（噻唑烷二酮或其衍生物）对PPARγ的最大活化促进原代人脂肪肉瘤细胞的终末分化。 还进一步发现RXR特异性配体在表达PPARγ/RXRα异源二聚体的细胞中也是有效的成脂剂，并且用噻唑烷二酰基部分（PPARγ选择性化合物）和RXR特异性同时治疗脂肪肉瘤细胞 配体导致分化的加性刺激。 因此，根据本发明，已经鉴定了可用于治疗脂肪肉瘤的组合物。

公开(公告)号：US06242196B1

公开(公告)日：2001-06-05

申请号：US09319769

申请日：1999-09-17

申请人： Bruce M. Spiegelman ,  Soner Altiok ,  Elisabetta Mueller ,  Pasha Sarraf ,  Peter Tontonoz

发明人： Bruce M. Spiegelman ,  Soner Altiok ,  Elisabetta Mueller ,  Pasha Sarraf ,  Peter Tontonoz

IPC分类号： C12Q134

CPC分类号： A61K31/426

摘要： A method for inhibiting proliferation of a PPAR &ggr;-responsive hyperproliferative cell which comprises the step of contacting the cell with (I) an inhibitory amount of a PPAR&ggr; agonist and (II) a MAP kinase inhibitor is disclosed. A method for treating or prophylactically preventing in an animal subject a disorder characterized by unwanted proliferation of PPAR&ggr;-responsive hyperproliferative cells which comprises administering to the subject (I) an inhibitory amount of a PPAR&ggr; agonist and (II) a MAP kinase inhibitor is also disclosed. Pharmaceutical compositions comprising a therapeutically effective amount of a PPAR&ggr; agonist and a MAP kinase inhibitor are disclosed for use in the methods.

摘要翻译： 公开了一种抑制PPARγ反应性过度增殖细胞增殖的方法，其包括使细胞与（I）抑制量的PPARγ激动剂和（II）MAP激酶抑制剂接触的步骤。 一种用于在动物受试者中治疗或预防性地预防PPARγ反应性过度增殖性细胞不希望的增殖的病症的方法，其包括对受试者（I）施用抑制量的PPARγ激动剂和（II）MAP激酶抑制剂 。 公开了包含治疗有效量的PPARγ激动剂和MAP激酶抑制剂的药物组合物用于该方法。

公开(公告)号：US06552055B2

公开(公告)日：2003-04-22

申请号：US08923346

申请日：1997-09-04

申请人： Bruce M. Spiegelman ,  Elisabetta Mueller ,  Pasha Sarraf ,  Soner Altiok ,  Peter Tontonoz ,  Samuel Singer

发明人： Bruce M. Spiegelman ,  Elisabetta Mueller ,  Pasha Sarraf ,  Soner Altiok ,  Peter Tontonoz ,  Samuel Singer

IPC分类号： A61K3144

CPC分类号： A61K45/06 ,  A61K31/426 ,  A61K31/427

摘要： The present invention is based on the finding that activation of PPAR&ggr; plays a key role in inducing growth arrest and differentiation of certain actively proliferating cells. We show that administration of PPAR&ggr; agonists, such as thiazolidinedione ligands (TZDs), is effective both in vitro and in vivo at inhibiting the proiferation of such cells.

公开(公告)号：US07635708B2

公开(公告)日：2009-12-22

申请号：US10324744

申请日：2002-12-19

申请人： Bruce M. Spiegelman ,  Elisabetta Mueller ,  Pasha Sarraf ,  Soner Altiok ,  Peter Tontonoz ,  Samuel Singer

发明人： Bruce M. Spiegelman ,  Elisabetta Mueller ,  Pasha Sarraf ,  Soner Altiok ,  Peter Tontonoz ,  Samuel Singer

IPC分类号： A61K31/675 ,  A61K31/41 ,  A61K31/425 ,  A61K31/28 ,  A61K33/24 ,  A01N57/00 ,  A01N43/82 ,  A01N43/78 ,  A01N55/02

CPC分类号： A61K31/425 ,  A61K31/426 ,  A61K31/427 ,  A61K45/06 ,  Y10S514/908

摘要： The present invention is based on the finding that activation of PPARγ plays a key role in inducing growth arrest and differentiation of certain actively proliferating cells. We show that administration of PPARγ agonists, such as thiazolidinedione ligands (TZDs), is effective both in vitro and in vivo at inhibiting the proliferation of such cells.

摘要翻译： 本发明基于以下发现：PPARγ的激活在诱导某些主动增殖细胞的生长停滞和分化中起关键作用。 我们显示PPARγ激动剂如噻唑烷二酮配体（TZD）的施用在体外和体内都有效抑制这些细胞的增殖。

公开(公告)号：US06646008B1

公开(公告)日：2003-11-11

申请号：US09331535

申请日：2000-02-22

申请人： Ronald M. Evans ,  Peter Tontonoz ,  Laszlo Nagy

发明人： Ronald M. Evans ,  Peter Tontonoz ,  Laszlo Nagy

IPC分类号： A61K3119

CPC分类号： A61K31/44 ,  A61K31/12 ,  A61K31/19 ,  A61K31/192 ,  A61K31/205 ,  A61K31/445 ,  A61K31/557 ,  A61K31/5575 ,  A61K2300/00

摘要： In accordance with the present invention, it has been discovered that PPAR&ggr; is expressed consistently in tissues associated with each of a variety of disease states which result from neoplastic cell proliferation. It has further been discovered that maximal activation of PPAR&ggr; with exogenous ligand promotes terminal differentiation of primary cells which are otherwise subject to neoplastic cell proliferation. In accordance with another aspect of the invention, it has been discovered that RXR-specific ligands are also potent agents for induction of differentiation of cells expressing the PPAR&ggr;/RXR&agr; heterodimer, and that simultaneous treatment of cells subject to neoplastic cell proliferation with a PPAR&ggr;-selective ligand, in combination with an RXR-specific ligand, results in an additive stimulation of differentiation. Thus, the effect of neoplastic cell proliferation can be ameliorated by treatment of cells undergoing neoplastic cell proliferation with PPAR&ggr; agonists, optionally in the further presence of RXR agonists, thereby blocking further proliferation thereof. Accordingly, compounds and compositions which are useful for the treatment of a variety of disease states which result from neoplastic cell proliferation have been identified and are described herein.

摘要翻译： 根据本发明，已经发现，PPARγ在与由肿瘤细胞增殖引起的各种疾病状态中的每一种相关的组织中一致地表达。 进一步发现，具有外源性配体的PPARγ的最大活化促进了另外受到肿瘤细胞增殖的原代细胞的终末分化。 根据本发明的另一方面，已经发现RXR特异性配体也是用于诱导表达PPARγ/RXRα异源二聚体的细胞分化的有效试剂，并且用PPARγ- 选择性配体与RXR特异性配体组合导致分化的加性刺激。 因此，可以通过用PPARγ激动剂处理经历赘生性细胞增殖的细胞，任选地在RXR激动剂的进一步存在下，可以改善肿瘤细胞增殖的作用，从而阻断其进一步增殖。 因此，已经鉴定并描述了可用于治疗由肿瘤细胞增殖引起的各种疾病状态的化合物和组合物。