公开(公告)号：US20150328192A1

公开(公告)日：2015-11-19

申请号：US14652825

申请日：2013-12-24

Applicant: THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM

Inventor： Maria E. GACZYNSKA ,  Pawel A. OSMULSKI

IPC: A61K31/436 ,  A61K45/06

CPC classification number: A61K31/436 ,  A61K31/453 ,  A61K31/69 ,  A61K45/06 ,  A61K2300/00

Abstract: The invention provides for treatment of cancers using a rapamycin analog, optionally including bortezomib. In particular, the invention addresses the treatment of bortezomib-resistant cancers using seco-rapamycin and optionally a second proteasome inhibitor. This invention relates to oncology and medicine, and more particularly to treatment of cancer. In particular, rapamycin analogs such as seco-rapamycin may be used advantageously to target the proteasome in cancer cells, optionally in conjunction with proteasome inhibitors such as bortezomib.

Abstract translation: 本发明提供了使用雷帕霉素类似物（任选地包括硼替佐米）治疗癌症。 特别地，本发明涉及使用次雷帕霉素和任选的第二蛋白酶体抑制剂治疗硼替佐米耐药性癌症。 本发明涉及肿瘤学和药物，更具体地涉及癌症的治疗。 特别地，雷帕霉素类似物例如雷帕霉素可有利地用于靶向癌细胞中的蛋白酶体，任选地与蛋白酶体抑制剂如硼替佐米结合。

公开(公告)号：US20160152567A1

公开(公告)日：2016-06-02

申请号：US14896984

申请日：2014-06-13

Applicant: THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM

Inventor： Pawel A. OSMULSKI ,  Maria E. GACZYNSKA

IPC: C07D211/60 ,  C07D498/08 ,  C07D413/12

CPC classification number: C07D211/60 ,  A61K31/69 ,  A61K45/06 ,  C07D401/12 ,  C07D413/12 ,  C07D498/08 ,  A61K2300/00

Abstract: The present invention relates generally to novel allosteric regulators of proteasome activity, methods for preparation and use, and pharmaceutical compositions thereof. Specifically piperidine-2-carboxylic acid derivatives containing 1-oxo-aroyl group and a lipophilic ester side chain are disclosed as allosteric inhibitors of proteasome 2S activity, and as therapeutic agents for the treatment of proteasome-associated disorders in a subject.

Abstract translation: 本发明一般涉及蛋白酶体活性的新型变构调节剂，其制备和使用方法及其药物组合物。 公开了具有1-氧代 - 芳酰基和亲脂性酯侧链的具体的哌啶-2-羧酸衍生物作为蛋白酶体2S活性的变构抑制剂，作为治疗受试者中蛋白酶体相关疾病的治疗剂。