公开(公告)号：US20060088471A1

公开(公告)日：2006-04-27

申请号：US11254541

申请日：2005-10-19

申请人： Mark Bennett ,  Tonia Buchholz ,  Susan Demo ,  Guy Laidig ,  Evan Lewis ,  Mark Smyth

发明人： Mark Bennett ,  Tonia Buchholz ,  Susan Demo ,  Guy Laidig ,  Evan Lewis ,  Mark Smyth

IPC分类号： A61K51/00 ,  C07K16/46 ,  C07K5/04 ,  C07K5/06

CPC分类号： C07K5/0812 ,  C07K1/13 ,  C07K5/06165 ,  C07K5/0806 ,  C07K5/0808 ,  C07K5/1016 ,  C12Q1/34 ,  C12Q1/37 ,  G01N33/573 ,  G01N2333/976 ,  G01N2500/00

摘要： Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like and PGPH activities of the 20S proteasome can be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus, such as a detectable label. Along with therapeutic utilities, these peptide based compounds can be used in assays useful for screening, monitoring, diagnostic and/or dosing purposes.

摘要翻译： 包括含杂原子的三元环的基于肽的化合物有效地选择性地抑制N末端亲核试剂（Ntn）水解酶的比活性。 具有多种活性的那些Ntn的活性可被所描述的化合物差别地抑制。 例如，本发明化合物可以选择性地抑制20S蛋白酶体的胰凝乳蛋白酶样和PGPH活性。 基于肽的化合物包括至少三种肽单元，环氧化物或氮丙啶，并且在N末端官能化，例如可检测标记。 与治疗用途一起，这些基于肽的化合物可用于用于筛选，监测，诊断和/或给药目的的测定中。

公开(公告)号：US20060193844A1

公开(公告)日：2006-08-31

申请号：US11365789

申请日：2006-02-28

申请人： Mark Bennett ,  Christopher Kirk ,  Susan Demo

发明人： Mark Bennett ,  Christopher Kirk ,  Susan Demo

IPC分类号： A61K38/54

CPC分类号： A61K31/40

摘要： Improved regimens for administering proteasome inhibitors are described, wherein proteasome inhibition is more sustained relative to certain current regimens which permit substantial recovery of proteasome activity between doses of inhibitor.

摘要翻译： 描述了用于施用蛋白酶体抑制剂的改进方案，其中蛋白酶体抑制相对于某些目前的方案更持续，其允许在剂量的抑制剂之间显着回收蛋白酶体活性。

公开(公告)号：US20060276489A1

公开(公告)日：2006-12-07

申请号：US11382445

申请日：2006-05-09

申请人： Dane Goff ,  Mark Bennett ,  Susan Demo

发明人： Dane Goff ,  Mark Bennett ,  Susan Demo

IPC分类号： A61K31/519

CPC分类号： C07D495/04

摘要： The invention relates to the inhibition of tubulin polymerization. The invention provides compounds and methods for inhibiting tubulin polymerization. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

摘要翻译： 本发明涉及微管蛋白聚合的抑制。 本发明提供了抑制微管蛋白聚合的化合物和方法。 本发明还提供了治疗细胞增殖性疾病和病症的组合物和方法。

公开(公告)号：US07071190B2

公开(公告)日：2006-07-04

申请号：US10369223

申请日：2003-02-18

申请人： Dane Goff ,  Mark K. Bennett ,  Susan Demo

发明人： Dane Goff ,  Mark K. Bennett ,  Susan Demo

IPC分类号： A61K31/535

CPC分类号： C07D495/04

摘要： The invention relates to the inhibition of tubulin polymerization. The invention provides compounds and methods for inhibiting tubulin polymerization. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

公开(公告)号：US07005254B2

公开(公告)日：2006-02-28

申请号：US10160663

申请日：2002-05-31

申请人： Susan Demo ,  Yasumichi Hitoshi ,  Denise Pearsall

发明人： Susan Demo ,  Yasumichi Hitoshi ,  Denise Pearsall

IPC分类号： C12Q1/00 ,  C12Q1/68 ,  G01N33/53

CPC分类号： C07K14/47 ,  G01N33/574 ,  G01N2333/705 ,  G01N2500/04

摘要： The present invention relates to regulation of cellular proliferation. More particularly, the present invention is directed to nucleic acids encoding LETM1 (“leucine zipper EF hand transmembrane receptor”), which is involved in modulation of cellular proliferation and cell cycle regulation. The invention further relates to methods for identifying and using agents, including small molecule chemical compositions, antibodies, siRNA, antisense nucleic acids, and ribozymes, that modulate cell cycle regulation and cellular proliferation via modulation of LETM1 and LETM1 related signal transduction; as well as to the use of expression profiles and compositions in diagnosis and therapy related to cell cycle regulation and modulation of cellular proliferation.

公开(公告)号：US5955354A

公开(公告)日：1999-09-21

申请号：US408519

申请日：1995-03-20

申请人： Lewis T. Williams ,  Susan Demo

发明人： Lewis T. Williams ,  Susan Demo

IPC分类号： A61K38/00 ,  C07K14/47 ,  C07H21/04 ,  A61K38/17 ,  C12N15/63 ,  C12N15/79

CPC分类号： C07K14/4702 ,  A61K38/00

摘要： A novel protein which interacts with ras p21, has been identified. This protein, RGL, shares 69% amino acid homology with ral guanine nucleotide dissociation stimulator (ralGDS). ralGDS was also found to bind ras p21. The ras p21-interacting domain of RGL (RID) bound to ras p21 through the effector loop of ras p21. Polypeptide and polynucleotide compositions of the RGL protein are provided as well as methods for implementing the diagnostic and therapeutic uses of these compositions. The uses include isolating effector proteins of ras p21 and modulating ras activity.

摘要翻译： 已经鉴定出与ras p21相互作用的新蛋白质。 该蛋白RGL与ral鸟嘌呤核苷酸解离刺激物（ralGDS）共享69％的氨基酸同源性。 还发现ralGDS与ras p21结合。 通过ras p21的效应环结合Ras p21的ras p21相互作用结构域（RID）与ras p21结合。 提供了RGL蛋白的多肽和多核苷酸组合物以及用于实施这些组合物的诊断和治疗用途的方法。 其用途包括分离ras p21的效应蛋白并调节ras活性。

公开(公告)号：US07413870B2

公开(公告)日：2008-08-19

申请号：US10026021

申请日：2001-12-21

申请人： Yasumichi Hitoshi ,  Susan Demo ,  Yonchu Jenkins

发明人： Yasumichi Hitoshi ,  Susan Demo ,  Yonchu Jenkins

IPC分类号： C12Q1/50

CPC分类号： G01N33/57484 ,  A61K38/00 ,  A61K2039/505 ,  G01N2333/912

摘要： The present invention relates to regulation of cellular proliferation. More particularly, the present invention is directed to nucleic acids encoding SAK, which is a protein kinase involved in modulation of cellular proliferation and cell cycle regulation. The invention further relates to methods for identifying and using agents, including small molecule chemical compositions, antibodies, peptides, cyclic peptides, nucleic acids, RNAi, antisense nucleic acids, and ribozymes, that modulate cell cycle regulation and cellular proliferation via modulation of SAK; as well as to the use of expression profiles and compositions in diagnosis and therapy related to cell cycle regulation and modulation of cellular proliferation, e.g., for treatment of cancer and other diseases of cellular proliferation.

摘要翻译： 本发明涉及细胞增殖的调控。 更具体地，本发明涉及编码SAK的核酸，其是参与调节细胞增殖和细胞周期调节的蛋白激酶。 本发明还涉及用于鉴别和使用通过调节SAK调节细胞周期调节和细胞增殖的试剂，包括小分子化学组合物，抗体，肽，环肽，核酸，RNAi，反义核酸和核酶的方法; 以及在细胞周期调控和细胞增殖调节相关的诊断和治疗中使用表达谱和组合物，例如用于治疗癌症和其它细胞增殖疾病。

公开(公告)号：US07358040B2

公开(公告)日：2008-04-15

申请号：US10026331

申请日：2001-12-21

申请人： Yasumichi Hitoshi ,  Susan Demo ,  Yonchu Jenkins

发明人： Yasumichi Hitoshi ,  Susan Demo ,  Yonchu Jenkins

IPC分类号： C12Q1/00

CPC分类号： C12Q1/34 ,  G01N33/5011 ,  G01N33/573 ,  G01N2333/922 ,  G01N2500/02

摘要： The present invention relates to regulation of cellular proliferation. More particularly, the present invention is directed to nucleic acids encoding MRE11, which is a protein involved in modulation of cellular proliferation. The invention further relates to methods for identifying and using agents, including small molecule chemical compositions, antibodies, peptides, cyclic peptides, nucleic acids, antisense nucleic acids, and ribozymes, that modulate cellular proliferation via modulation of MRE11; as well as to the use of expression profiles and compositions in diagnosis and therapy related to modulation of cellular proliferation.

摘要翻译： 本发明涉及细胞增殖的调控。 更具体地，本发明涉及编码MRE11的核酸，其是涉及细胞增殖调节的蛋白质。 本发明还涉及用于鉴定和使用通过调节MRE11来调节细胞增殖的试剂，包括小分子化学组合物，抗体，肽，环肽，核酸，反义核酸和核酶的方法; 以及在与调节细胞增殖相关的诊断和治疗中使用表达谱和组合物。