公开(公告)号：WO2002059267A2

公开(公告)日：2002-08-01

申请号：PCT/US2002/001701

申请日：2002-01-23

Applicant: DUKE UNIVERSITY

Inventor： BARAK, Larry, S. ,  OAKLEY, Robert, H. ,  CARON, Marc, G. ,  LAPORTE, Stephane, A. ,  WILBANKS, Alyson

IPC: C12N

CPC classification number: A61K31/64 ,  A01K2217/05 ,  A61K31/41 ,  A61K38/00 ,  C07K14/705 ,  C07K14/723

Abstract: The present invention relates to modified G-protein coupled receptors (GPCRs). The modified GPCRs of the present invention include GPCRs that have been modified to have altered DRY motifs such that the modified GPCRs are constitutively desensitized. As such, the modified GPCRs of the present invention preferably localize to endocytic vesicles or endosomes in an agonist-independent manner. The invention also relates to methods of screening compounds and sample solutions for GPCR activity using the modified GPCRs.

Abstract translation: 本发明涉及修饰的G蛋白偶联受体（GPCR）。 本发明的修饰的GPCR包括已被修饰为具有改变的DRY基序的GPCR，使得修饰的GPCRs被组成型脱敏。 因此，本发明的修饰的GPCR优选以不依赖于激动剂的方式定位于内吞囊泡或内体。 本发明还涉及使用修饰的GPCR筛选化合物和GPCR活性的样品溶液的方法。

公开(公告)号：WO2003088924A2

公开(公告)日：2003-10-30

申请号：PCT/US2003/008208

申请日：2003-03-18

Applicant: DUKE UNIVERSITY ,  ROCKMAN, Howard, A. ,  NAGA PRASAD, Sathyamangla, V. ,  LAPORTE, Stephane, A. ,  BARAK, Larry, S. ,  CARON, Marc, G.

Inventor： ROCKMAN, Howard, A. ,  NAGA PRASAD, Sathyamangla, V. ,  LAPORTE, Stephane, A. ,  BARAK, Larry, S. ,  CARON, Marc, G.

IPC: A61K

CPC classification number: A01K67/0275 ,  A01K2217/05 ,  G01N33/566 ,  G01N2333/726 ,  G01N2500/10

Abstract: The present invention relates to compounds that alter GPCR internalization and new methods for their identification. Compounds of this invention include modified phosphoinositide 3-kinase (PI3K), modified HEAT domain, modified -adrenergic receptor kinase 1 ( ARK1), as well as other peptides or small molecules that alter GPCR internalization. The present invention also includes the use of such compounds to treat GPCR-related diseases, such as cardiovascular disease, heart failure, asthma, nephrogenic diabetes insipidus, or hypertension.

Abstract translation: 本发明涉及改变GPCR内化的化合物及其鉴定方法。 本发明的化合物包括修饰的磷酸肌醇3-激酶（PI3K），修饰的HEAT结构域，修饰的 - 肾上腺素能受体激酶1（ARK1），以及改变GPCR内化的其它肽或小分子。 本发明还包括使用这些化合物治疗GPCR相关疾病，例如心血管疾病，心力衰竭，哮喘，肾源性尿崩症或高血压。

公开(公告)号：WO2003088924A3

公开(公告)日：2003-10-30

申请号：PCT/US2003/008208

申请日：2003-03-18

Applicant: DUKE UNIVERSITY ,  ROCKMAN, Howard, A. ,  NAGA PRASAD, Sathyamangla, V. ,  LAPORTE, Stephane, A. ,  BARAK, Larry, S. ,  CARON, Marc, G.

Inventor： ROCKMAN, Howard, A. ,  NAGA PRASAD, Sathyamangla, V. ,  LAPORTE, Stephane, A. ,  BARAK, Larry, S. ,  CARON, Marc, G.

IPC: C12Q1/00

Abstract: The present invention relates to compounds that alter GPCR internalization and new methods for their identification. Compounds of this invention include modified phosphoinositide 3-kinase (PI3K), modified HEAT domain, modified -adrenergic receptor kinase 1 ( ARK1), as well as other peptides or small molecules that alter GPCR internalization. The present invention also includes the use of such compounds to treat GPCR-related diseases, such as cardiovascular disease, heart failure, asthma, nephrogenic diabetes insipidus, or hypertension.