公开(公告)号：US20120088300A1

公开(公告)日：2012-04-12

申请号：US12679406

申请日：2010-02-05

申请人： Douglas A. Melton ,  Malgorzata Borowiak ,  Rene Maehr ,  Shuibing Chen ,  Weiping Tang ,  Julia L. Fox ,  Stuart L. Schreiber

发明人： Douglas A. Melton ,  Malgorzata Borowiak ,  Rene Maehr ,  Shuibing Chen ,  Weiping Tang ,  Julia L. Fox ,  Stuart L. Schreiber

IPC分类号： C12N5/071 ,  C07C251/86 ,  C07C251/84

CPC分类号： C12N5/0678 ,  C12N5/0603 ,  C12N5/0606 ,  C12N2501/999 ,  C12N2506/02 ,  C12N2506/03

摘要： Certain embodiments disclosed herein are directed to a method of producing endoderm cells, such as definitive endoderm cells by exposing stem cells such as embryonic stem cells or induced pluripotent stem (iPS) cells to an effective amount of at least one compound described herein to differentiate the stem cells into the endoderm cells such as definitive endoderm cells. Differentated endoderm cells produced by the methods disclosed herein can be differentiated into pancreatic epithelium, and other endoderm derivatives such as thymus, liver, stomach, intestine and lung. Another aspect of the present invention relates to a method of producing pancreatic progenitor cells, such as Pdx1-positive pancreatic progenitor cells by exposing endoderm cells, such as definitive endoderm cells to an effective amount of at least one compound described herein to differentiate the definitive endoderm cells into Pdx1-positive pancreatic progenitor cells. Kits and compositions comprising Pdx1-positive pancreatic progenitor produced using the methods are also described.

摘要翻译： 本文公开的某些实施例涉及通过将干细胞如胚胎干细胞或诱导的多能干（iPS）细胞暴露于有效量的本文所述的至少一种化合物来分化本发明的内胚层细胞，例如定形内胚层细胞， 干细胞进入内胚层细胞，如定形内胚层细胞。 通过本文公开的方法产生的分化的内胚层细胞可以分化成胰腺上皮和其它内胚层衍生物如胸腺，肝，胃，肠和肺。 本发明的另一方面涉及通过将内胚层细胞如定形内胚层细胞暴露于有效量的至少一种本文所述的化合物来分化定形内胚层来产生胰腺祖细胞如Pdx1阳性胰腺祖细胞的方法 细胞进入Pdx1阳性胰腺祖细胞。 还描述了使用该方法制备的包含Pdx1阳性胰腺祖细胞的组合物和组合物。

公开(公告)号：US20110313045A1

公开(公告)日：2011-12-22

申请号：US13221561

申请日：2011-08-30

申请人： Stuart L. Schreiber ,  Jack Taunton ,  Christian A. Hassig ,  Timothy F. Jamison

发明人： Stuart L. Schreiber ,  Jack Taunton ,  Christian A. Hassig ,  Timothy F. Jamison

IPC分类号： A61K31/16 ,  C07C259/06 ,  A61P35/00 ,  C12N5/071

CPC分类号： C12N9/80 ,  A01K2217/05 ,  A01K2217/075 ,  A61K31/00 ,  A61K31/165 ,  A61K31/407 ,  A61K38/00 ,  A61K48/00 ,  C07K5/126 ,  C07K14/4702 ,  C07K14/4703 ,  C07K2319/00 ,  C12N9/16

摘要： The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

摘要翻译： 本发明涉及由一系列基因（称为HDx相关基因）编码的蛋白质的发现，其涉及染色质结构的控制，因此涉及转录和翻译。 本发明提供可用于例如在体外和体内控制细胞增殖和分化的组合物和方法。

公开(公告)号：US07932213B2

公开(公告)日：2011-04-26

申请号：US10370885

申请日：2003-02-20

申请人： Seung Bum Park ,  David Barnes-Seeman ,  Angela N. Koehler ,  Stuart L. Schreiber

发明人： Seung Bum Park ,  David Barnes-Seeman ,  Angela N. Koehler ,  Stuart L. Schreiber

IPC分类号： C40B40/04 ,  C40B30/04 ,  C40B50/08 ,  C40B60/04 ,  G01N33/566 ,  G01N33/543 ,  G01N33/53

CPC分类号： C40B60/14 ,  B01J19/0046 ,  B01J2219/00387 ,  B01J2219/00454 ,  B01J2219/00459 ,  B01J2219/005 ,  B01J2219/00533 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/00626 ,  B01J2219/00637 ,  B01J2219/0072 ,  C07B2200/11 ,  C07C311/49 ,  C40B30/04 ,  C40B40/04 ,  C40B50/14 ,  G01N33/54353 ,  Y10S436/809

摘要： The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. A composition is provided that comprises an array of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm2. The inventive arrays are generated by: providing a solid support functionalized with a selected chemical moiety capable of interacting with a chemical compound to form an attachment and delivering compounds to the solid support having a density of at least 1000 spots per cm2. The present invention also provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest.

摘要翻译： 本发明提供了有助于鉴定能够与感兴趣的生物大分子相互作用的化合物的组合物和方法。 提供了包含连接到固体支持物上的化学化合物阵列的组合物，其中化合物阵列的密度为每cm 2至少1000个点。 本发明的阵列通过以下方式产生：提供用选择的能够与化学化合物相互作用的选择的化学部分官能化的固体支持物，以形成连接并将化合物输送到具有至少1000个点/ cm 2的密度的固体支持物。 本发明还提供了利用这些阵列鉴定感兴趣的生物大分子的小分子配偶体的方法。

公开(公告)号：US20110003385A1

公开(公告)日：2011-01-06

申请号：US12684784

申请日：2010-01-08

申请人： Gerald R. Crabtree ,  Stuart L. Schreiber ,  David M. Spencer ,  Thomas J. Wandless ,  Steffan N. Ho ,  Peter Belshaw

发明人： Gerald R. Crabtree ,  Stuart L. Schreiber ,  David M. Spencer ,  Thomas J. Wandless ,  Steffan N. Ho ,  Peter Belshaw

IPC分类号： C12N5/07 ,  C12N15/63 ,  C12N15/12

CPC分类号： C07K14/705 ,  A61K38/00 ,  A61K47/6425 ,  C07D498/18 ,  C07F5/025 ,  C07H19/01 ,  C07K7/645 ,  C07K14/395 ,  C07K14/7051 ,  C07K14/71 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C07K2319/035 ,  C07K2319/09 ,  C07K2319/20 ,  C07K2319/32 ,  C07K2319/42 ,  C07K2319/43 ,  C07K2319/60 ,  C07K2319/71 ,  C07K2319/715 ,  C07K2319/81 ,  C07K2319/90 ,  C12N15/1055 ,  C12N15/62 ,  C12N15/63 ,  C12N15/67 ,  C12P15/00

摘要： Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. In principle, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands. To illustrate the practice of this invention, we have induced: (1) the intracellular aggregation of the cytoplasmic tail of the ζ chain of the T cell receptor (TCR)-CD3 complex thereby leading to signaling and transcription of a reporter gene, (2) the homodimerization of the cytoplasmic tail of the Fas receptor thereby leading to cell-specific apoptosis (programmed cell death) and (3) the heterodimerization of a DNA-binding domain (Gal4) and a transcription-activation domain (VP16) thereby leading to direct transcription of a reporter gene.Regulated intracellular protein association with our cell permeable, synthetic ligands offers new capabilities in biological research and medicine, in particular, in gene therapy.

摘要翻译： 蛋白质的二聚化和寡聚化是促进细胞膜受体，转录因子，囊泡融合蛋白和其他类型的细胞外和细胞外蛋白质的活化的一般生物学控制机制。 我们已经开发了细胞内蛋白质的调节（诱导型）二聚化或寡聚化的一般程序。 原则上，任何两种靶蛋白都可以通过用含有细胞可渗透的合成配体处理带有它们的细胞或生物来诱导相关联。 为了说明本发明的实践，我们已经诱导：（1）T细胞受体（TCR）-CD3复合物的ζ链的细胞质尾部的细胞内聚集，从而导致报告基因的信号传导和转录（2 ）Fas受体的细胞质尾的同源二聚体，从而导致细胞特异性凋亡（程序性细胞死亡）和（3）DNA结合结构域（Gal4）和转录激活结构域（VP16）的异二聚化，从而导致 直接转录报告基因。 调节的细胞内蛋白与我们的细胞可渗透合成配体的关联提供了生物研究和医学，特别是基因治疗方面的新​​功能。

公开(公告)号：US20080311589A1

公开(公告)日：2008-12-18

申请号：US12107042

申请日：2008-04-21

申请人： Brent R. Stockwell ,  Stuart L. Schreiber ,  Timothy J. Mitchison ,  Tarun M. Kapoor ,  Thomas Mayer ,  Stephen J. Haggarty

发明人： Brent R. Stockwell ,  Stuart L. Schreiber ,  Timothy J. Mitchison ,  Tarun M. Kapoor ,  Thomas Mayer ,  Stephen J. Haggarty

IPC分类号： G01N33/53

CPC分类号： G01N33/6803

摘要： The present invention provides a system for high-throughput analysis of chemical compounds. Assays are performed in a high density platform, and compounds having pre-determined desirable effects are identified. Preferably, the compounds have biological effects, more preferably, the assays and detection are performed on whole cells.

摘要翻译： 本发明提供了化合物的高通量分析系统。 测定在高密度平台中进行，并且鉴定了具有预定的期望效果的化合物。 优选地，化合物具有生物学效应，更优选地，测定和检测在全细胞上进行。

公开(公告)号：US06982082B1

公开(公告)日：2006-01-03

申请号：US08922240

申请日：1997-08-27

申请人： Stuart L. Schreiber ,  Peter J. Belshaw ,  Gerald Crabtree

发明人： Stuart L. Schreiber ,  Peter J. Belshaw ,  Gerald Crabtree

IPC分类号： A61K48/00 ,  C12N5/00 ,  C12N15/00 ,  C12N15/63 ,  C12N15/74

CPC分类号： A61K48/005 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0325 ,  A01K2267/035 ,  C07K7/645 ,  C12N9/90 ,  C12N15/8509 ,  C12N2830/008

摘要： This invention is directed to a modified cyclosporin A and to a modified, genetically engineered version of its receptor, cyclophilin. This invention is further directed to a method for treating host versus graft disease following blood marrow transplantation by transfecting stem cells so that after introduction into a patient the stem cells will express the modified cyclophilin, and, as necessary, administer the modified cyclosporin A to the patient.

摘要翻译： 本发明涉及改良的环孢菌素A及其受体，亲环蛋白的修饰的基因工程版本。 本发明还涉及一种通过转染干细胞来治疗血液骨髓移植后的宿主与移植物疾病的方法，使得在引入患者之后，干细胞将表达经修饰的亲环蛋白，并且根据需要将修饰的环孢菌素A施用于 患者。

公开(公告)号：US06777217B1

公开(公告)日：2004-08-17

申请号：US08624735

申请日：1996-03-26

申请人： Stuart L. Schreiber ,  Jack Taunton ,  Christian A. Hassig ,  Timothy F. Jamison

发明人： Stuart L. Schreiber ,  Jack Taunton ,  Christian A. Hassig ,  Timothy F. Jamison

IPC分类号： C12N912

CPC分类号： C12N9/80 ,  A01K2217/05 ,  A01K2217/075 ,  A61K31/00 ,  A61K31/165 ,  A61K31/407 ,  A61K38/00 ,  A61K48/00 ,  C07K5/126 ,  C07K14/4702 ,  C07K14/4703 ,  C07K2319/00 ,  C12N9/16

摘要： The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

摘要翻译： 本发明涉及由一系列基因（称为HDx相关基因）编码的蛋白质的发现，其涉及染色质结构的控制，因此涉及转录和翻译。 本发明提供可用于例如在体外和体内控制细胞增殖和分化的组合物和方法。

公开(公告)号：US06335358B1

公开(公告)日：2002-01-01

申请号：US08421583

申请日：1995-04-12

申请人： Gabriel Fenteany ,  Timothy F. Jamison ,  Stuart L. Schreiber ,  Robert F. Standaert

发明人： Gabriel Fenteany ,  Timothy F. Jamison ,  Stuart L. Schreiber ,  Robert F. Standaert

IPC分类号： A61K3136

CPC分类号： C07D487/04 ,  A61K31/4015 ,  A61K31/407 ,  C07D491/10 ,  C07D495/10 ,  C12N9/6421

摘要： Compounds related to lactacystin and lactacystin &bgr;-lactone, pharmaceutical compositions containing the compounds, and methods of use.

摘要翻译： 与乳胞素和乳胞蛋白β-内酯相关的化合物，含有这些化合物的药物组合物和使用方法。

公开(公告)号：US06140120A

公开(公告)日：2000-10-31

申请号：US158010

申请日：1998-09-16

申请人： Gerald R. Crabtree ,  Stuart L. Schreiber ,  David M. Spencer ,  Thomas J. Wandless ,  Steffan N. Ho ,  Peter Belshaw

发明人： Gerald R. Crabtree ,  Stuart L. Schreiber ,  David M. Spencer ,  Thomas J. Wandless ,  Steffan N. Ho ,  Peter Belshaw

IPC分类号： A61K38/00 ,  A61K47/48 ,  C07D498/18 ,  C07F5/02 ,  C07H19/01 ,  C07K7/64 ,  C07K14/395 ,  C07K14/705 ,  C07K14/71 ,  C07K14/725 ,  C12N15/62 ,  C12N15/63 ,  C12P15/00 ,  C12N5/10

CPC分类号： C07D498/18 ,  A61K47/48276 ,  C07F5/025 ,  C07H19/01 ,  C07K14/395 ,  C07K14/705 ,  C07K14/7051 ,  C07K14/71 ,  C07K7/645 ,  C12N15/62 ,  C12N15/63 ,  C12P15/00 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C07K2319/035 ,  C07K2319/09 ,  C07K2319/20 ,  C07K2319/32 ,  C07K2319/42 ,  C07K2319/43 ,  C07K2319/60 ,  C07K2319/71 ,  C07K2319/715 ,  C07K2319/81 ,  C07K2319/90

摘要： Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. In principle, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands. To illustrate the practice of this invention, we have induced: (1) the intracellular aggregation of the cytoplasmic tail of the .xi. chain of the T cell receptor (TCR)-CD3 complex thereby leading to signalig and transcription of a reporter gene, (2) the homodimerization of the cytoplasmic tail of the Fas receptor thereby leading to cell-specific apoptosis (programmed cell death) and (3) the heterodimerization of a DNA-binding domain (Gal4) and a transcription-activation domain (VP16) thereby leading to direct transcription of a reporter gene. Regulated intracellular protein association with our cell permeable, synthetic ligands offers new capabilities in biological research and medicine, in particular, in gene therapy. Using gene transfer techniques to introduce our artificial receptors, one can turn on or off the signaling pathways that lead to the overexpression of therapeutic proteins by administering orally active "dimerizers" or "de-dimerizers", respectively. Since cells from different recipients can be configured to have the pathway overexpress different therapeutic proteins for use in a variety of disorders, the dimerizers have the potential to serve as "universal drugs". They can also be viewed as cell permeable, organic replacements for therapeutic antisense agents or for proteins that would otherwise require intravenous injection or intracellular expression (e.g., the LDL receptor or the CFTR protein).

公开(公告)号：US5994313A

公开(公告)日：1999-11-30

申请号：US483898

申请日：1995-06-07

申请人： Gerald R. Crabtree ,  Stuart L. Schreiber ,  David M. Spencer ,  Thomas J. Wandless ,  Peter Belshaw

发明人： Gerald R. Crabtree ,  Stuart L. Schreiber ,  David M. Spencer ,  Thomas J. Wandless ,  Peter Belshaw

IPC分类号： A61K38/00 ,  A61K47/48 ,  A61K48/00 ,  A61P43/00 ,  C07D498/18 ,  C07F5/02 ,  C07H19/01 ,  C07K7/64 ,  C07K14/395 ,  C07K14/705 ,  C07K14/71 ,  C07K14/715 ,  C07K14/725 ,  C12N15/62 ,  C12N15/63 ,  C12P15/00 ,  C12P17/18 ,  A61K31/70 ,  A61K38/13 ,  C12N5/10

CPC分类号： C07D498/18 ,  A61K47/48276 ,  A61K48/00 ,  C07F5/025 ,  C07H19/01 ,  C07K14/395 ,  C07K14/705 ,  C07K14/7051 ,  C07K14/71 ,  C07K14/715 ,  C07K7/645 ,  C12N15/62 ,  C12N15/63 ,  C12P15/00 ,  C12P17/188 ,  A01K2217/05 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C07K2319/035 ,  C07K2319/09 ,  C07K2319/20 ,  C07K2319/32 ,  C07K2319/42 ,  C07K2319/43 ,  C07K2319/60 ,  C07K2319/71 ,  C07K2319/715 ,  C07K2319/81 ,  C07K2319/90

摘要： We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells.