公开(公告)号：US20160074400A1

公开(公告)日：2016-03-17

申请号：US14419646

申请日：2013-08-06

Applicant: University of Southern California ,  Albert Einstein College of Medicine of Yeshiva University

Inventor： Michael Kahn ,  Chandan Guha ,  Subhrajit Saha ,  Payel Bhanja

IPC: A61K31/519 ,  A61K38/17 ,  C12N7/00 ,  A61K45/06

CPC classification number: A61K31/519 ,  A61K38/1709 ,  A61K45/06 ,  C12N5/0679 ,  C12N7/00 ,  C12N2501/415 ,  C12N2501/998 ,  C12N2501/999 ,  C12N2710/10043 ,  C12N2710/10071 ,  A61K2300/00

Abstract: Provided are composition and methods for treating radiation-induced cell damage, and in particular aspects to methods for protecting, mitigating or otherwise treating radiation-induced induced depletion of tissue stem cells and injury to the supportive stem cell niche, and in even more particular aspects to methods for protecting, mitigating or otherwise treating radiation-induced gastrointestinal syndrome (RIGS), comprising sequential administration of a Wnt pathway activator/agonist (e.g., Rspo1 or a small molecule inducer thereof) that amplifies the surviving intestinal stem cell (ISC) pool post-radiation exposure, followed by a selective antagonist of the β-Catenin-CBP interaction (e.g., ICG-001 or other exemplary compounds disclosed herein) that accelerates differentiation of the stimulated (e.g., Rspo1-stimulated) ISC in crypt-villi axis, promoting villous regeneration and intestinal restitution, thereby mitigating RIGS. Adjunctive and combination therapy embodiments are encompassed.

Abstract translation: 提供了用于治疗放射诱导的细胞损伤的组合物和方法，特别是涉及用于保护，减轻或以其它方式治疗辐射诱导的组织干细胞诱导的耗竭和支持性干细胞利基的损伤的方法，并且在更具体的方面 涉及用于保护，减轻或以其它方式治疗放射诱导的胃肠道综合征（RIGS）的方法，包括顺序施用放大存活的肠干细胞（ISC）池的Wnt途径激活剂/激动剂（例如，Rspo1或其小分子诱导剂） 辐射后暴露，然后是加速受体（例如，Rspo1刺激的）ISC在隐窝绒毛中的分化的＆amp; -Cenin-CBP相互作用的选择性拮抗剂（例如，ICG-001或本文公开的其它示例性化合物） 轴线，促进绒毛再生和肠道恢复，从而减轻RIGS。 包括辅助和联合治疗实施例。

公开(公告)号：US20150306177A1

公开(公告)日：2015-10-29

申请号：US14666746

申请日：2015-03-24

Applicant: ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY

Inventor： Chandan Guha ,  Subhrajit Saha

IPC: A61K38/17

CPC classification number: A61K38/1709 ,  A61K35/761 ,  A61K48/00 ,  A61K48/005 ,  A61K48/0083 ,  C07K14/075 ,  C07K14/435 ,  C07K14/4702 ,  C12N2710/10343

Abstract: Methods are disclosed for therapy of radiation-induced lung injury and other lung diseases using R-spondin1.

Abstract translation: 公开了使用R-spondin1治疗放射诱导的肺损伤和其它肺部疾病的方法。