公开(公告)号：WO2007035641A3

公开(公告)日：2007-03-29

申请号：PCT/US2006/036295

申请日：2006-09-15

Applicant: ARIZONA BOARD OF REGENTS, ACTING ON BEHALF OF THE UNIVERSITY OF ARIZONA ,  UNIVERSITY OF PITTSBURGH ,  POWIS, Garth ,  WIPF, Peter

Inventor： POWIS, Garth ,  WIPF, Peter

IPC: A61K31/12 ,  A61K31/335

Abstract: Embodiments of the present invention relate to inhibitors of thioredoxin. Certain embodiments relate to palmarumycin based compounds and methods of using the same. Such compounds may be useful in inhibiting the overexpression of thioredoxin, inhibiting tumor growth and treating cancer.

公开(公告)号：WO2005007828A2

公开(公告)日：2005-01-27

申请号：PCT/US2004/022656

申请日：2004-07-14

Applicant: PROLX PHARMACEUTICALS, INC. ,  ARIZONA BOARD OF REGENTS, ACTING ON BEHALF OF THE UNIVERSITY OF ARIZONA ,  KIRKPATRICK, Lynn ,  POWIS, Garth ,  WELSH, Sarah, J.

Inventor： KIRKPATRICK, Lynn ,  POWIS, Garth ,  WELSH, Sarah, J.

IPC: C12N

CPC classification number: A61K31/66

Abstract: The hypoxia inducible factor-1 (HIF-1) transcription factor is an important regulator of the cellular response to hypoxia. The activity of HIF-1 is regulated by the level of the HIF-l α subunit, HIF-l α, which is rapidly degraded under normoxic conditions by the ubiquitin-proteasome pathway. HIF-lα levels increase under hypoxic conditions. Many human cancers also show constitutively increased HIF-lα levels. PX-478 or S-2-amino-3­[4'-N,N,-bis(2-chloroethyl) amino]phenyl propionic acid N-oxide dihydrochloride, is a novel anticancer agent, and is capably of decreasing both constitutive and hypoxia induced HIF-1α protein levels and H1F-1 transactivation in vitro and in vivo. In method embodiments, the administration of PX-478 is independent of the pathways of HIF-lα regulation involving the von Hippel-Lindau protein and p53. PX-478 causes an increase in polyubiquitinated HIF-lα levels due to inhibition of HIF-lα deubiquitination. The levels of other proteins whose proteasomal breakdown is mediated by ubiquitination are not affected by PX-478. Deubiquitination is a novel pathway for the regulation of cellular HIF-1α levels and PX-478 is a specific inhibitor of the pathway. Therapeutic compounds for regulating cellular HIF-1α levels and methods of regulating cellular HIF-1α levels are herein provided

Abstract translation: 缺氧诱导因子-1（HIF-1）转录因子是细胞对缺氧反应的重要调节因子。 HIF-1的活性由HIF-1α亚基HIF-1α的水平调节，HIF-1α在含氧量正常的条件下被泛素 - 蛋白酶体途径迅速降解。 低氧条件下HIF-1α水平增加。 许多人类癌症也显示组成型增加的HIF-1α水平。 PX-478或S-2-氨基-3'-shy; [4'-N，N， - 双（2-氯乙基）氨基]苯基丙酸N-氧化物二盐酸盐，是一种新型的抗癌剂， 和缺氧在体内和体外诱导HIF-1α蛋白水平和H1F-1反式激活。 在方法实施方案中，PX-478的施用独立于涉及von Hippel-Lindau蛋白和p53的HIF-1α调节途径。 由于HIF-1α去泛素化的抑制，PX-478引起多聚泛素化HIF-1α水平的增加。 其他蛋白质的蛋白酶体降解是由泛素介导的，不受PX-478影响。 去泛素化是调节细胞HIF-1α水平的新途径，PX-478是途径的特异性抑制剂。 本文提供了用于调节细胞HIF-1α水平的治疗性化合物和调节细胞HIF-1α水平的方法。

公开(公告)号：WO2007008200A1

公开(公告)日：2007-01-18

申请号：PCT/US2005/024429

申请日：2005-07-11

Applicant: PROLX PHARMACEUTICALS CORP. ,  ARIZONA BOARD OF REGENTS, ACTING ON BEHALF OF THE UNIVERSITY OF ARIZONA ,  UNIVERSITY OF PITTSBURGH ,  KIRKPATRICK, Lynn ,  POWIS, Garth ,  WIPF, Peter

Inventor： KIRKPATRICK, Lynn ,  POWIS, Garth ,  WIPF, Peter

IPC: A61K31/40 ,  A61K31/35 ,  C07D311/78

CPC classification number: C07D311/78 ,  A61K31/337 ,  A61K31/35 ,  A61K31/366 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/7072 ,  A61K33/24 ,  A61K45/06 ,  C07D311/94 ,  A61K2300/00

Abstract: wortmannin analogs and their use in inhibiting PI-3-kinase activity in mammals and the treatment of cancer and tumor formation in a subject are described herein, ehich may be administered with other chemotherapeutic agents in the treatment of cancer.

Abstract translation: 本文描述了渥曼青霉素类似物及其在抑制哺乳动物中的PI-3-激酶活性和治疗受试者中癌症和肿瘤形成的用途，其可以与其它化学治疗剂一起施用于治疗癌症。

公开(公告)号：WO2004043359A2

公开(公告)日：2004-05-27

申请号：PCT/US2003/035226

申请日：2003-11-03

Applicant: PROLX PHARMACEUTICALS CORPORATION ,  ARIZONA BOARD OF REGENTS, ACTING ON BEHALF OF THE UNIVERSITY OF ARIZONA ,  KIRKPATRICK, Lynn ,  POWIS, Garth ,  WELSH, Sarah, J.

Inventor： KIRKPATRICK, Lynn ,  POWIS, Garth ,  WELSH, Sarah, J.

IPC: A61K

CPC classification number: A61K31/66 ,  A61K31/195 ,  C07F9/65846

Abstract: This invention relates to compounds which are N-oxides and derivatives thereof, as well as their use to treat HIF related diseases. These compounds have the general formula set out below and are used to treat a variety of diseases associated with HIF: formula (I) wherein R is an alkyl, aryl, arakyl or derivatives thereof such as CH3OCH2CH2- , CH3 CH2OCH2CH2- , C6H5OCH2CH2- , C6H5CH2- , CH3 (CH2)3OCH2CH2Cl; or any one of the following: formula (II), (III) and (IV).

Abstract translation: 本发明涉及作为N-氧化物及其衍生物的化合物及其用于治疗HIF相关疾病的用途。 这些化合物具有下列通式，用于治疗与HIF相关的各种疾病：式（I）其中R是烷基，芳基，芳基或其衍生物，例如CH 3 OCH 2 CH 2 - ，CH 3 CH 2 OCH 2 CH 2 - ，C 6 H 5 OCH 2 CH 2 - C 6 H 5 CH 2 - ，CH 3（CH 2）3 OCH 2 CH 2 Cl; 或以下任何一种：式（II），（III）和（IV）。

公开(公告)号：WO2009052467A1

公开(公告)日：2009-04-23

申请号：PCT/US2008/080429

申请日：2008-10-20

Applicant: BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM ,  ARIZONA BOARD OF REGENTS, ACTING ON BEHALF OF THE UNIVERSITY OF ARIZONA ,  POWIS, Garth ,  IHLE, Nathan

Inventor： POWIS, Garth ,  IHLE, Nathan

IPC: G01N33/50

CPC classification number: G01N33/5091 ,  A61K31/366 ,  A61K31/685 ,  A61K31/7064 ,  A61K31/7105

Abstract: The invention described herein is directed to methods for identifying an individual who may be resistant or susceptible to phosphatidylinositol-3-kinase inhibitors, methods of treating an individual by identifying individuals who are resistant or susceptible to phosphatidylinositol-3-kinase inhibitors, and kits for testing individuals for resistance or susceptibility to phosphatidylinositol-3-kinase inhibitors.

Abstract translation: 本文描述的发明涉及用于鉴定可能对磷脂酰肌醇-3-激酶抑制剂具有抗性或易感性的个体的方法，通过鉴定对磷脂酰肌醇-3-激酶抑制剂具有抗性或易感性的个体来治疗个体的方法，以及用于 测试个体对磷脂酰肌醇-3-激酶抑制剂的抗药性或易感性。

公开(公告)号：WO2004024093A2

公开(公告)日：2004-03-25

申请号：PCT/US2003/028920

申请日：2003-09-15

Applicant: ARIZONA BOARD OF REGENTS, ACTING ON BEHALF OF THE UNIVERSITY OF ARIZONA ,  POWIS, Garth ,  ABRAHAM, Robert

Inventor： POWIS, Garth ,  ABRAHAM, Robert

IPC: A61K

CPC classification number: C07D311/94 ,  A61K31/35 ,  A61K31/40

Abstract: A method of inhibiting restenosis in a subject following coronary angioplasty atherectomy, or arterial bypass graft surgery comprised of administering wortmannin analogs of the present invention is described herein.

Abstract translation: 本文描述了冠状动脉成形术粥样斑块切除术后抑制受试者再狭窄的方法，或包含本发明施用渥曼青霉素类似物的动脉旁路移植手术。