公开(公告)号：US20160022708A1

公开(公告)日：2016-01-28

申请号：US14774380

申请日：2014-03-13

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

Inventor： Kevin Freeman

IPC: A61K31/655 ,  A61K31/635 ,  A61K31/404 ,  A61K45/06 ,  A61K31/167

CPC classification number: A61K31/655 ,  A61K31/167 ,  A61K31/404 ,  A61K31/635 ,  A61K45/06 ,  A61K2300/00

Abstract: Provided herein are methods for a novel combination therapy for treating a glutamine-addicted cancer in a subject in need thereof, which comprises the administration of a glutaminase antagonist and a pro-apoptotic compound. Specific glutaminase antagonists and pro-apoptotic compounds are provided. In some embodiments, the glutaminase antagonist is 6-diazo-5-oxo-1-norleucine (DON) and the pro-apoptotic compound is a Bcl-2 family member antagonist. In some embodiments, the pro-apoptotic compound is obatoclax mesylate, navitoclax, or fenretinide. In some embodiments, the glutamine-addicted cancer is a cancer in which Myc is deregulated. In some embodiments, the cancer is a pediatric cancer.

Abstract translation: 本文提供了用于治疗有需要的受试者中的谷氨酰胺上瘾癌症的新型联合疗法的方法，其包括施用谷氨酰胺酶拮抗剂和促凋亡化合物。 提供特异性谷氨酰胺酶拮抗剂和促凋亡化合物。 在一些实施方案中，谷氨酰胺酶拮抗剂是6-重氮-5-氧代-1-正亮氨酸（DON），促凋亡化合物是Bcl-2家族成员拮抗剂。 在一些实施方案中，促凋亡化合物是甲磺酸盐，纳米复合体或芬维A胺。 在一些实施方案中，谷氨酰胺上瘾的癌症是其中Myc被释放调节的癌症。 在一些实施方案中，癌症是儿科癌症。