公开(公告)号：WO2005024058A2

公开(公告)日：2005-03-17

申请号：PCT/EP2004/010172

申请日：2004-09-10

Applicant: GALAPAGOS GENOMICS N.V. ,  MERCHIERS, Pascal, Gerard ,  SPITTAELS, Koenraad, Frederik, Florentina ,  HOFMANN, Marcel ,  THIJS, Kim ,  LAENEN, Wendy

Inventor： MERCHIERS, Pascal, Gerard ,  SPITTAELS, Koenraad, Frederik, Florentina ,  HOFMANN, Marcel ,  THIJS, Kim ,  LAENEN, Wendy

IPC: C12Q1/68

CPC classification number: C12N15/113 ,  A61K38/00 ,  C07K7/06 ,  C07K14/605 ,  C07K14/705 ,  C12N15/1138 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/53 ,  C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/6896 ,  G01N2800/2821

Abstract: The present invention relates to compounds for use as a medicament in diseases involving cognitive impairment such as Alzheimer’s disease. In particular, the present invention relates to antagonists of and translation inhibitory compounds of the gene encoding FPRL1, FPRL2, FPR1, GPR32, CMKLR1, C5R1, GPR44, GCGR, GLP1R, GLP2R, GIPR, VIPR1, SCTR, VIPR2, providing a reduction of the levels of amyloid-beta protein. The invention further relates to methods for identifying such agonists and translation inhibitory compounds and methods for diagnosing a pathological condition involving cognitive impairment.

Abstract translation: 本发明涉及用作涉及认知障碍（例如阿尔茨海默氏病）的疾病的药物的化合物。 具体而言，本发明涉及编码FPRL1，FPRL2，FPR1，GPR32，CMKLR1，C5R1，GPR44，GCGR，GLP1R，GLP2R，GIPR，VIPR1，SCTR，VIPR2的基因的拮抗剂和翻译抑制化合物， 淀粉样蛋白-β蛋白的水平。 本发明进一步涉及鉴定此类激动剂和翻译抑制化合物的方法和用于诊断涉及认知障碍的病理状态的方法。

公开(公告)号：WO2005103715A3

公开(公告)日：2006-08-03

申请号：PCT/EP2005051882

申请日：2005-04-26

Applicant: GALAPAGOS NV ,  SPITTAELS KOENRAAD FREDERIK FL ,  HOFFMANN MARCEL ,  MERCHIERS PASCAL GERARD

Inventor： SPITTAELS KOENRAAD FREDERIK FL ,  HOFFMANN MARCEL ,  MERCHIERS PASCAL GERARD

IPC: G01N33/68 ,  A61K48/00 ,  A61P25/28 ,  C07K14/665 ,  C12N15/113

CPC classification number: C12N15/1138 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/53 ,  G01N2333/4709 ,  G01N2500/04

Abstract: A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a melanocortin receptor polypeptide, or fragment thereof, and measuring a compound-polypeptide property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including second messenger and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of melanocortin receptor inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.

Abstract translation: 一种用于鉴定抑制细胞中淀粉样蛋白β前体蛋白处理的化合物的方法，包括使测试化合物与黑皮质素受体多肽或其片段接触，并测量与淀粉状蛋白-β肽的产生相关的化合物 - 多肽性质。 该方法的细胞测定法测量包括第二信使和/或淀粉样蛋白β肽水平的指标。 包括有效的淀粉样蛋白β前体加工抑制量的黑皮质素受体抑制剂的治疗方法和药物组合物可用于治疗涉及认知障碍的疾病如阿尔茨海默病。

公开(公告)号：WO2005119262A2

公开(公告)日：2005-12-15

申请号：PCT/EP2005/052421

申请日：2005-05-27

Applicant: GALAPAGOS GENOMICS N.V. ,  MERCHIERS, Pascal Gerard ,  HINNEKINT, Sofie ,  SPITTAELS, Koenraad Frederik Florentina

Inventor： MERCHIERS, Pascal Gerard ,  HINNEKINT, Sofie ,  SPITTAELS, Koenraad Frederik Florentina

IPC: G01N33/68

CPC classification number: G01N33/6896

Abstract: A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a HIT polypeptide, or fragment thereof, and measuring a compound-HIT property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including cleaved protease substrates, phosphorylated kinase substrate, second messenger levels and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of HIT expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimer's disease.

Abstract translation: 一种用于鉴定抑制细胞中淀粉样蛋白β前体蛋白加工的化合物的方法，包括使测试化合物与HIT多肽或其片段接触，并测量与淀粉状蛋白-β肽的产生相关的化合物-HIT性质。 所述方法的细胞测定测量指标包括切割的蛋白酶底物，磷酸化激酶底物，第二信使水平和/或淀粉样蛋白β肽水平。 包括有效的淀粉样蛋白-β前体加工抑制量的HIT表达抑制剂的治疗方法和药物组合物可用于治疗涉及认知障碍的疾病如阿尔茨海默病。

公开(公告)号：WO2005024058A3

公开(公告)日：2005-11-10

申请号：PCT/EP2004010172

申请日：2004-09-10

Applicant: GALAPAGOS GENOMICS NV ,  MERCHIERS PASCAL GERARD ,  SPITTAELS KOENRAAD FREDERIK FL ,  HOFMANN MARCEL ,  THIJS KIM ,  LAENEN WENDY

Inventor： MERCHIERS PASCAL GERARD ,  SPITTAELS KOENRAAD FREDERIK FL ,  HOFMANN MARCEL ,  THIJS KIM ,  LAENEN WENDY

IPC: A61K38/00 ,  C07K7/06 ,  C07K14/605 ,  C07K14/705 ,  C07K14/72 ,  C12N15/113 ,  C12Q1/68 ,  G01N33/566 ,  G01N33/68 ,  A61K48/00

CPC classification number: C12N15/113 ,  A61K38/00 ,  C07K7/06 ,  C07K14/605 ,  C07K14/705 ,  C12N15/1138 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/53 ,  C12Q1/6883 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/6896 ,  G01N2800/2821

Abstract: The present invention relates to compounds for use as a medicament in diseases involving cognitive impairment such as Alzheimer's disease. In particular, the present invention relates to antagonists of and translation inhibitory compounds of the gene encoding FPRL1, FPRL2, FPR1, GPR32, CMKLR1, C5R1, GPR44, GCGR, GLP1R, GLP2R, GIPR, VIPR1, SCTR, VIPR2, providing a reduction of the levels of amyloid-beta protein. The invention further relates to methods for identifying such agonists and translation inhibitory compounds and methods for diagnosing a pathological condition involving cognitive impairment.

Abstract translation: 本发明涉及在涉及认知障碍（例如阿尔茨海默病）的疾病中用作药物的化合物。 特别地，本发明涉及编码FPRL1，FPRL2，FPR1，GPR32，CMKLR1，C5R1，GPR44，GCGR，GLP1R，GLP2R，GIPR，VIPR1，SCTR，VIPR2的基因和翻译抑制化合物的拮抗剂， 淀粉样蛋白-β蛋白的水平。 本发明还涉及用于鉴定此类激动剂和翻译抑制化合物的方法以及用于诊断涉及认知功能障碍的病理状态的方法。

公开(公告)号：WO2005103707A1

公开(公告)日：2005-11-03

申请号：PCT/EP2004/005625

申请日：2004-05-21

Applicant: GALAPAGOS GENOMICS N.V. ,  SPITTAELS, Koenraad, Frederik, Florentina ,  HOFFMANN, Marcel ,  MERCHIERS, Pascal, Gerard

Inventor： SPITTAELS, Koenraad, Frederik, Florentina ,  HOFFMANN, Marcel ,  MERCHIERS, Pascal, Gerard

IPC: G01N33/68

CPC classification number: C12N15/111 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/53 ,  C12N2320/12 ,  G01N33/6896 ,  G01N33/74 ,  G01N2333/4709 ,  G01N2800/2821

Abstract: The present invention relates to methods of identifying compounds that influence the amyloid-beta precursor protein processing in a cell, and/or that influence the activity or levels of proteins involved in the processing of the amyloid beta precursor protein. It furthermore relates to the compounds that may be identified using the methods of the invention and to use of said compounds in the treatment of neurological disorders such as Alzheimer's disease. More specifically, it relates to compounds that target the AVPR1a, AVPR1b and/or AVPR2 receptors.

Abstract translation: 本发明涉及鉴定影响细胞中淀粉样蛋白β前体蛋白处理的化合物的方法和/或影响参与淀粉样蛋白β前体蛋白的加工的蛋白质的活性或水平的方法。 它还涉及可以使用本发明的方法鉴定的化合物和所述化合物在治疗神经障碍如阿尔茨海默氏病中的用途。 更具体地说，它涉及靶向AVPR1a，AVPR1b和/或AVPR2受体的化合物。

公开(公告)号：WO2005103692A2

公开(公告)日：2005-11-03

申请号：PCT/EP2005/004323

申请日：2005-04-20

Applicant: GALAPAGOS GENOMICS N.V. ,  MERCHIERS, Pascal, Gerard ,  SPITTAELS, Koenraad, Frederik, Florentina

Inventor： MERCHIERS, Pascal, Gerard ,  SPITTAELS, Koenraad, Frederik, Florentina

IPC: G01N33/50

CPC classification number: C12N15/1137 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2799/022 ,  C12Q1/485 ,  C12Y207/01091 ,  G01N33/6896 ,  G01N2500/04 ,  G01N2500/10

Abstract: A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a SPHK polypeptide, or fragment thereof, and measuring a compound-SPHK property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including phosphorylated kinase substrate and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of SPHK expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimer’s Disease.

Abstract translation: 用于鉴定抑制细胞中淀粉样蛋白β前体蛋白处理的化合物的方法，包括使测试化合物与SPHK多肽或其片段接触，并测量与淀粉状蛋白-β肽的产生相关的化合物-SPHK性质。 所述方法的细胞测定法包括磷酸化激酶底物和/或淀粉状蛋白β肽水平。 包括有效淀粉样蛋白β前体加工抑制量的SPHK表达抑制剂的治疗方法和药物组合物可用于治疗涉及认知障碍的症状如阿尔茨海默病。

公开(公告)号：WO2005103689A1

公开(公告)日：2005-11-03

申请号：PCT/EP2004/005624

申请日：2004-05-21

Applicant: GALAPAGOS GENOMICS N.V. ,  SPITTAELS, Koenraad, Frederik, Florentina ,  HOFFMANN, Marcel ,  MERCHIERS, Pascal, Gerard

Inventor： SPITTAELS, Koenraad, Frederik, Florentina ,  HOFFMANN, Marcel ,  MERCHIERS, Pascal, Gerard

IPC: G01N33/50

CPC classification number: G01N33/6896 ,  G01N2333/4709 ,  G01N2333/726 ,  G01N2500/10 ,  G01N2800/2821

Abstract: The present invention relates to methods of identifying compounds that influence the amyloid-beta precursor protein processing in a cell, and/or that influence the activity or levels of proteins involved in the processing of the amyloid beta precursor protein. It furthermore relates to the compounds that may be identified using the methods of the invention and to use of said compounds in the treatment of neurological disorders such as Alzheimer's disease. More specifically, it relates to compounds that target the melanocortin 3 and 4 receptors (MC3R and MC4R).

Abstract translation: 本发明涉及鉴定影响细胞中淀粉样蛋白β前体蛋白处理的化合物的方法和/或影响参与淀粉样蛋白β前体蛋白的加工的蛋白质的活性或水平的方法。 它还涉及可以使用本发明的方法鉴定的化合物和所述化合物在治疗神经障碍如阿尔茨海默氏病中的用途。 更具体地说，它涉及靶向黑皮质素3和4受体（MC3R和MC4R）的化合物。

公开(公告)号：WO2008101985A3

公开(公告)日：2008-10-16

申请号：PCT/EP2008052119

申请日：2008-02-21

Applicant: ABLYNX NV ,  MERCHIERS PASCAL GERARD ,  VERHEESEN PETER ,  HOOGENBOOM HENDRICUS RENERUS J

Inventor： MERCHIERS PASCAL GERARD ,  VERHEESEN PETER ,  HOOGENBOOM HENDRICUS RENERUS J

IPC: C07K16/22

CPC classification number: C07K16/22 ,  C07K2317/22 ,  C07K2317/569 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92

Abstract: The present invention relates to amino acid sequences that are directed against vascular endothelial growth factor (VEGF), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. The amino acid sequences, compounds and constructs can be used for prophylactic, therapeutic or diagnostic purposes, such as for the treatment of conditions and diseases characterized by excessive and/or pathological angiogenesis or neovascularization.

Abstract translation: 本发明涉及针对血管内皮生长因子（VEGF）以及包含或基本上由一个或多个这样的氨基酸序列组成的化合物或构建体，特别是蛋白质和多肽的氨基酸序列。 氨基酸序列，化合物和构建体可用于预防，治疗或诊断目的，例如用于治疗以过度和/或病理性血管生成或新生血管形成为特征的病症和疾病。

公开(公告)号：WO2005109000A3

公开(公告)日：2006-09-14

申请号：PCT/EP2005052173

申请日：2005-05-12

Applicant: GALAPAGOS NV ,  LAENEN WENDY ,  SPITTAELS KOENRAAD FREDERIK FL ,  HOFFMANN MARCEL ,  MERCHIERS PASCAL GERARD

Inventor： SPITTAELS KOENRAAD FREDERIK FL ,  HOFFMANN MARCEL ,  MERCHIERS PASCAL GERARD

IPC: G01N33/68 ,  A61K48/00 ,  C12Q1/00 ,  C12Q1/25 ,  C12Q1/48 ,  C12Q1/68 ,  G01N20060101 ,  G01N33/53 ,  G01N33/567 ,  G01N33/74

CPC classification number: C12Q1/37 ,  A61K48/00 ,  C12Q1/25 ,  C12Q1/485 ,  G01N33/6896 ,  G01N33/74 ,  G01N2333/4709 ,  G01N2333/726 ,  G01N2333/9015 ,  G01N2500/00 ,  G01N2500/02 ,  G01N2500/04 ,  G01N2800/2821

Abstract: A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a GPCR polypeptide GRPR, ADRA1A, TACR1, or fragment thereof, and measuring a compound-GPCR property related to the production of amyloid-beta peptide. Celluler assays of the method measure indicators including second messenger and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of GPCR expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.

Abstract translation: 一种用于鉴定抑制细胞中淀粉样蛋白β前体蛋白加工的化合物的方法，包括使测试化合物与GPCR多肽GRPR，ADRA1A，TACR1或其片段接触，并测量与淀粉样蛋白-β产生相关的化合物-GPCR性质 肽。 该方法的细胞测定法测量包括第二信使和/或淀粉样蛋白β肽水平的指标。 包括有效的淀粉样蛋白-β前体加工抑制量的GPCR表达抑制剂的治疗方法和药物组合物可用于治疗涉及认知障碍的疾病如阿尔茨海默病。

公开(公告)号：WO2005103713A3

公开(公告)日：2006-09-08

申请号：PCT/EP2005004325

申请日：2005-04-20

Applicant: GALAPAGOS NV ,  MERCHIERS PASCAL GERARD ,  SPITTAELS KOENRAAD FREDERIK FL ,  HOFFMANN MARCEL

Inventor： MERCHIERS PASCAL GERARD ,  SPITTAELS KOENRAAD FREDERIK FL ,  HOFFMANN MARCEL

IPC: G01N33/68 ,  A61K48/00 ,  A61P25/28 ,  C12N15/00 ,  C12Q1/37 ,  G01N33/53 ,  G01N33/566 ,  G01N33/567

CPC classification number: C12Q1/37 ,  G01N33/566 ,  G01N33/6896 ,  G01N2333/4709 ,  G01N2333/726 ,  G01N2500/00 ,  G01N2800/2821

Abstract: A method for identifying compounds that inhibit amyloid-beta precursor protein processing in cells, comprising contacting a test compound with a GPCR polypeptide, (eg. GPR3, GPR6, GPR12) or fragment thereof, and measuring a compound-GPCR property related to the production of amyloid-beta peptide. Cellular assays of the method measure indicators including second messenger and/or amyloid beta peptide levels. Therapeutic methods, and pharmaceutical compositions including effective amyloid-beta precursor processing-inhibiting amounts of GPCR expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.

Abstract translation: 一种用于鉴定抑制细胞中淀粉样蛋白β前体蛋白加工的化合物的方法，包括使测试化合物与GPCR多肽（例如GPR3，GPR6，GPR12）或其片段接触，并测量与生产相关的化合物GPCR性质 的淀粉样蛋白-β肽。 该方法的细胞测定法测量包括第二信使和/或淀粉样蛋白β肽水平的指标。 包括有效的淀粉样蛋白-β前体加工抑制量的GPCR表达抑制剂的治疗方法和药物组合物可用于治疗涉及认知障碍的疾病如阿尔茨海默病。