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    Rab7 GTPase inhibitors and related methods of treatment
    5.
    发明授权
    Rab7 GTPase inhibitors and related methods of treatment 有权
    Rab7 GTPase抑制剂及相关治疗方法

    公开(公告)号：US09376452B2

    公开(公告)日：2016-06-28

    申请号：US14278468

    申请日：2014-05-15

    Applicant: STC.UNM ,  UNIVERSITY OF KANSAS

    Inventor： Angela Wandinger-Ness ,  Larry Sklar ,  Jacob Agola ,  Zurab Surviladze ,  Jeffrey Aube ,  Jennifer Golden ,  Chad E. Schroeder ,  Denise S. Simpson

    IPC: C07D495/04 ,  A61K31/381 ,  A61K45/06

    CPC classification number: C07D495/04 ,  A61K31/381 ,  A61K45/06

    Abstract: This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.

    Abstract translation: 本发明涉及化合物及其作为Rab7 GTPase的抑制剂或活化剂的用途，用于治疗或预防Rab 7 GTP酶相关疾病如神经病变，癌症，骨骼和脂质储存代谢疾病的发生。 本发明也适用于Rab7灭活或其蛋白质 - 蛋白质相互作用被调节以促进病原体的细胞内存活的感染性疾病。 所描述的化合物作为核苷酸结合的竞争性抑制剂，因此也可用作靶向其他小GTP酶的支架。 一方面，本发明的治疗方法用于治疗或预防遗传性感觉神经病发作，例如Charcot-Marie-Tooth 2B型疾病。 还提供了相关的药物组合物，测定和药物筛选。

    Modulators of GTPase and Use In Relevant Treatment
    6.
    发明申请
    Modulators of GTPase and Use In Relevant Treatment 有权
    GTPase调节剂和相关治疗用途

    公开(公告)号：US20130345277A1

    公开(公告)日：2013-12-26

    申请号：US13867658

    申请日：2013-04-22

    Applicant: STC.UNM ,  Kansas University Center for Technology Commercialization, Inc.

    Inventor： Angela Wandinger-Ness ,  Larry Sklar ,  Zurab Surviladze ,  Tudor Oprea ,  Laurie Hudson ,  Jeffrey Aube ,  Jennifer E. Golden ,  Chad E. Schroeder ,  Denise S. Simpson ,  Julica J. Noth

    IPC: A61K31/415 ,  A61K45/06 ,  C07D231/06

    CPC classification number: A61K31/407 ,  A61K31/403 ,  A61K31/415 ,  A61K45/06 ,  C07D231/06 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/573 ,  Y02A50/473 ,  Y02A50/486 ,  A61K2300/00

    Abstract: The present invention relates to molecules which function as selective modulators of the Ras-homologous (Rho) family of small GTPases, in particular, Cdc42 GTPase and their use to treat diseases, for example cancers, including metastatic cancer, genetic and acquired diseases where activation of Cdc42 GTPase plays a pivotal role, such as neurodegenerative diseases, rheumatoid arthritis, atherosclerosis, diabetes type I, autosomal polycystic kidney disease, cystic kidney disease, precystic kidney disease, microbial infections, including Chlamydia infections, E. coli infections, H. pylori infections and its secondary effects including gastric ulcers, Coxiella Brunetti (Q-fever) infections and Streptococcus pneumonia infections, fungal infections including Paracoccidiodes brasiliensis and Candida albicans and their secondary effects including lung edema. Additionally, compounds according to the present invention may be used to inhibit rejection in transplant patients (pursuant to transplantation), to promote immunosuppression, anti-inflammatory response and to mobilize stem cell (migration) in patients in need, among others.

    Abstract translation: 本发明涉及用作小GTP酶的Ras同源（Rho）家族，特别是Cdc42GTP酶的选择性调节剂的分子及其用于治疗疾病的用途，例如癌症，包括转移性癌症，遗传和获得性疾病，其中激活 的Cdc42 GTPase起着关键的作用，如神经退行性疾病，类风湿关节炎，动脉粥样硬化，I型糖尿病，常染色体多囊肾病，囊性肾病，前期肾脏疾病，微生物感染，包括衣原体感染，大肠杆菌感染，幽门螺杆菌 感染及其次要作用包括胃溃疡，布氏梭菌（Qex fever）感染和肺炎链球菌感染，包括巴西隐孢子虫和白色念珠菌在内的真菌感染及其副作用，包括肺水肿。 此外，根据本发明的化合物可以用于抑制移植患者的排斥（根据移植），以促进免疫抑制，抗炎反应和在需要的患者中调动干细胞（迁移）等。

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