公开(公告)号：WO2018022494A1

公开(公告)日：2018-02-01

申请号：PCT/US2017/043481

申请日：2017-07-24

Applicant: STC.UNM

Inventor： TIMMINS, Graham ,  LIU, Ke Jian Jim ,  ZHOU, Xixi

IPC: A61K31/395 ,  A61K45/06 ,  A61P31/06

Abstract: The present invention is directed to the discovery that pyrazinamide, a potent anti-tuberculosis agent acts through an entirely unexpected mechanism- through inhibition of the host enzyme poly ADP ribose polymerase ("PARP"). Thus, the present invention is directed to methods of treating: mycobacterial infections ( Mycobacterium ), especially M. tuberculosis using a PARP inhibitor, optionally in combination with at least one additional agent useful in the treatment of a mycobacterial infection, especially tuberculosis. Pharmaceutical compositions, especially including a pharmaceutical composition in oral or inhalation dosage form, comprising a PARP inhibitor, optionally in combination with an additional anti-mycobacterial agent, especially an additional anti-tuberculosis agent represent additional embodiments of the present invention.

Abstract translation: 本发明涉及通过抑制宿主酶多聚ADP核糖聚合酶（“PARP”）而发现吡嗪酰胺（一种有效的抗结核剂）通过完全意想不到的机制起作用。 因此，本发明涉及治疗：分枝杆菌感染（分枝杆菌），特别是M的方法。 任选地与至少一种可用于治疗分枝杆菌感染，特别是结核病的其他药剂组合使用。 包含PARP抑制剂的药物组合物，特别是包含口服或吸入剂型的药物组合物，任选地与另外的抗分枝杆菌剂，特别是另外的抗结核剂组合，代表本发明的另外的实施方案。

公开(公告)号：WO2014152330A1

公开(公告)日：2014-09-25

申请号：PCT/US2014/027218

申请日：2014-03-14

Applicant: STC.UNM ,  LIU, Ke, Jian Jim ,  HUDSON, Laurie ,  COOPER, Karen ,  ZHOU, Xixi

Inventor： LIU, Ke, Jian Jim ,  HUDSON, Laurie ,  COOPER, Karen ,  ZHOU, Xixi

IPC: A61P35/00

CPC classification number: A61K33/36 ,  A61K31/166 ,  A61K31/407 ,  A61K31/4184 ,  A61K31/4188 ,  A61K31/454 ,  A61K31/502 ,  A61K31/5025 ,  A61K31/55 ,  A61K31/555 ,  A61K31/7068 ,  A61K41/0038 ,  A61K45/06 ,  A61N2005/1098 ,  A61K2300/00

Abstract: In one embodiment, the invention provides a method of treating a subject who suffers from a cancer (particularly a chemotherapeutic or radiotherapeutic-resistant cancer) or from an inflammatory disorder, the method comprising co-administering to the subject a pharmaceutically-effective amount of: (a) one or more elements or compounds selected from the group consisting of arsenic, an arsenite and arsenic trioxide (ATO); and optionally (b) at least one anticancer agent (preferably a DNA damaging agent); and/or (c) at least one or more Poly(ADP-ribose) polymerase (PARP) inhibitors other than arsenic, an arsenite and arsenic trioxide (ATO). In preferred embodiments, the arsenic for the treatment of cancer, arsenite and ATO serve as radio sensitizers for concomitant radiotherapy as well as PARP inhibitors. Methods for treating inflammatory disease are also disclosed. Related pharmaceutical formulations are also provided.

Abstract translation: 在一个实施方案中，本发明提供了治疗患有癌症（特别是化学治疗或放射治疗耐药性癌症）或炎症性疾病的受试者的方法，所述方法包括向受试者共同施用药物有效量的： （a）选自砷，亚砷酸钠和三氧化二砷（ATO）中的一种或多种元素或化合物; 和（b）至少一种抗癌剂（优选DNA损伤剂）; 和/或（c）至少一种或多种除砷以外的聚（ADP-核糖）聚合酶（PARP）抑制剂，亚砷酸钠和三氧化二砷（ATO））。 在优选的实施方案中，用于治疗癌症，亚砷酸盐和ATO的砷用作伴随放疗的放射敏化剂以及PARP抑制剂。 还公开了治疗炎性疾病的方法。 还提供了相关的药物制剂。