公开(公告)号：US06255069B1

公开(公告)日：2001-07-03

申请号：US08464954

申请日：1995-06-06

申请人： Jeffrey L. Benovic ,  Jorge Gomez ,  Priya Kunapuli

发明人： Jeffrey L. Benovic ,  Jorge Gomez ,  Priya Kunapuli

IPC分类号： C12N1512

CPC分类号： C12N9/1205 ,  C12N2799/026

摘要： G protein-coupled receptor kinases (GRK) play an important role in phosphorylating and regulating the activity of G protein-coupled receptors. Complementary DNAs (cDNAs) that encode two novel members of the G protein-coupled receptor kinase (GRK) family are provided in the present invention. These cDNAs encode GRK5 (590 amino acids) and GRK6 (576 amino acids) which represent two new members of the GRK family that have distinct tissue distribution and substrate specificity. The availability of the cDNAs enables the generation of reagents to modulate the activity of endogenous kinases. These include dominant negative mutations and antisense oligonucleotides or stably transfected antisense constructs to block expression of the kinase to generate a cell with a reduced ability to desensitize to various agents. Expression of GRK5 and GRK6 also permits identification of specific inhibitors and activators of these two kinases. Such inhibitors and activators may be used therapeutically to either directly modulate the activity of a given receptor or by augmenting the ability of a given therapeutic agent to stimulate a given receptor.

摘要翻译： G蛋白偶联受体激酶（GRK）在磷酸化和调节G蛋白偶联受体的活性中起重要作用。 在本发明中提供了编码G蛋白偶联受体激酶（GRK）家族的两个新成员的互补DNA（cDNA）。 这些cDNA编码GRK5（590个氨基酸）和GRK6（576个氨基酸），其代表具有不同组织分布和底物特异性的GRK家族的两个新成员。 cDNA的可用性使得能够产生用于调节内源性激酶活性的试剂。 这些包括显性阴性突变和反义寡核苷酸或稳定转染的反义构建体以阻断激酶的表达以产生具有降低对各种试剂的敏感能力的细胞。 GRK5和GRK6的表达还可以鉴定这两种激酶的特异性抑制剂和活化剂。 这样的抑制剂和活化剂可以用于治疗性地直接调节给定受体的活性或增加给定治疗剂刺激给定受体的能力。

公开(公告)号：US20080027095A1

公开(公告)日：2008-01-31

申请号：US11794400

申请日：2006-01-03

申请人： Priya Kunapuli ,  Berta Strulovici

发明人： Priya Kunapuli ,  Berta Strulovici

IPC分类号： A61K31/439 ,  A61P25/04 ,  G01N33/00

CPC分类号： A61K31/4745 ,  G01N33/74 ,  G01N2333/726 ,  G01N2800/2842 ,  Y10T436/145555

摘要： The invention encompasses a method for treating a disease or condition mediated by the human MRG-X1 receptor, such as nociception, hyperalgesia, allodynia, pain related to central hypersensitivity conditions, somatic pain, visceral pain, acute pain, chronic pain, post-operative pain, headache, inflammatory pain, neurological pain, musculoskeletal pain, cancer related pain or vascular pain, in a human patient in need thereof comprising administering to the patient a therapeutically effective amount of a 3-substituted-2-(diphenylmethy)-1-azabicyclo[2.2.2]octane or a pharmaceutically acceptable salt thereof. The invention is also directed to the use of these compounds as molecular tools to directly explore the role of the MRG-X1 receptor in pain perception.

摘要翻译： 本发明包括用于治疗由人类MRG-X1受体介导的疾病或病症的方法，例如伤害感受，痛觉过敏，异常性疼痛，与中枢性超敏反应性病症相关的疼痛，体细胞疼痛，内脏痛，急性疼痛，慢性疼痛，术后 疼痛，头痛，炎性疼痛，神经性疼痛，肌肉骨骼疼痛，癌症相关的疼痛或血管疼痛，包括向患者施用治疗有效量的3-取代-2-（二苯基甲基）-1- 氮杂二环[2.2.2]辛烷或其药学上可接受的盐。 本发明还涉及这些化合物作为分子工具直接探索MRG-X1受体在疼痛感知中的作用的用途。