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公开(公告)号:US6090544A
公开(公告)日:2000-07-18
申请号:US764522
申请日:1996-12-12
IPC分类号: C12N15/09 , A61K31/00 , A61K38/00 , A61K38/27 , A61K45/00 , A61P1/00 , A61P1/04 , A61P1/16 , A61P9/00 , A61P9/10 , A61P19/00 , A61P19/08 , A61P25/28 , A61P29/00 , A61P43/00 , C07K14/51 , C12N15/12 , C12Q1/68 , C12N5/10 , C12N15/11
摘要: Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.
摘要翻译: 本文公开了用于鉴定形态发生类似物的方法和组合物。 优选的方法和组合物涉及小鼠X型胶原启动子活性的形态发生上调由MEF-2样序列介导并需要相邻的AP-1序列的发现。 某些方法依赖于使用测试细胞,其包括定义与报告基因可操作地相关的形态发生反应性转录激活元件的DNA。 其他方法依赖于使用DNA来测量形态发生诱导型DNA结合。 在某些优选的实施方案中,所述方法和DNA涉及成骨蛋白1(OP-1)响应转录激活元件。 介导与OP-1反应性转录激活元件的相互作用和/或激活的物质在本文中被认为可能用于再现诸如OP-1的形态发生体的作用。
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公开(公告)号:US07306903B1
公开(公告)日:2007-12-11
申请号:US09613177
申请日:2000-07-10
IPC分类号: C12Q1/68
CPC分类号: C07K14/4705 , A61K38/00 , C07K14/51
摘要: Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.
摘要翻译: 本文公开了用于鉴定形态发生类似物的方法和组合物。 优选的方法和组合物涉及小鼠X型胶原启动子活性的形态发生上调由MEF-2样序列介导并需要相邻的AP-1序列的发现。 某些方法依赖于使用测试细胞,其包括定义与报告基因可操作地相关的形态发生反应性转录激活元件的DNA。 其他方法依赖于使用DNA来测量形态发生诱导型DNA结合。 在某些优选的实施方案中,所述方法和DNA涉及成骨蛋白1(OP-1)响应转录激活元件。 介导与OP-1反应性转录激活元件的相互作用和/或激活的物质在本文中被认为可能用于再现诸如OP-1的形态发生体的作用。
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公开(公告)号:US5834188A
公开(公告)日:1998-11-10
申请号:US507598
申请日:1995-07-26
IPC分类号: C12N15/09 , A61K31/00 , A61K38/00 , A61K38/27 , A61K45/00 , A61P1/00 , A61P1/04 , A61P1/16 , A61P9/00 , A61P9/10 , A61P19/00 , A61P19/08 , A61P25/28 , A61P29/00 , A61P43/00 , C07K14/51 , C12Q1/68 , C12N5/00 , C12Q1/02
摘要: Disclosed herein are methods and compositions for identifying morphogen analogs. Preferred methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. In certain embodiments, the methods involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.
摘要翻译: 本文公开了用于鉴定形态发生类似物的方法和组合物。 优选的方法在于使用测试细胞,所述测试细胞包含限定与报告基因操作相关的形态发生反应性转录激活元件的DNA。 在某些实施方案中,所述方法涉及成骨蛋白1(OP-1)响应转录激活元件。 本文认为激活OP-1反应性转录激活元件的物质可能用于再现诸如OP-1的形态发生体的作用。
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公开(公告)号:US06645974B2
公开(公告)日:2003-11-11
申请号:US10205634
申请日:2002-07-25
申请人: John H. Hutchinson , Michael J. Breslin , Gideon A. Rodan , Soumya P. Sahoo , Mark E. Duggan , Shun-Ichi Harada , Azriel Schmidt , Wasyl Halczenko , Dwight A. Towler
发明人: John H. Hutchinson , Michael J. Breslin , Gideon A. Rodan , Soumya P. Sahoo , Mark E. Duggan , Shun-Ichi Harada , Azriel Schmidt , Wasyl Halczenko , Dwight A. Towler
IPC分类号: A61K3158
CPC分类号: C07J73/005 , A61K31/435 , A61K31/473 , A61K31/58 , C07D221/18 , C07D401/12 , C07D405/12 , C07D409/12
摘要: Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of agonizing the androgen receptor in a patient, and in particular the method wherein the androgen receptor is antagonized in the prostate of a male patient or in the uterus of a female patient and agonized in bone and/or muscle tissue. These compounds are useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including: osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, arthritis and joint repair, alone or in combination with other active agents. In addition, these compounds are useful as pharmaceutical composition ingredients alone and in combination with other active agents.
摘要翻译: 公开了本文定义的结构式(I)的化合物可用于在需要这种调节的患者中以组织选择性方式调节雄激素受体的方法,以及在患者中激动雄激素受体的方法 ,特别是其中雄性受体在男性患者的前列腺或女性患者的子宫中被拮抗并在骨和/或肌肉组织中激动的方法。 这些化合物可用于治疗由雄激素缺乏引起的或可由雄激素施用而改善的病症,包括:骨质疏松症,牙周病,骨折,骨重建手术后的骨损伤,肌肉减少症,虚弱,衰老皮肤,男性性腺机能减退 妇女的绝经症状,动脉粥样硬化,高胆固醇血症,高脂血症,再生障碍性贫血和其他造血障碍,胰腺癌,肾癌,关节炎和关节修复,单独或与其他活性剂组合。 此外,这些化合物可单独用作药物组合物成分并与其它活性剂组合使用。
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公开(公告)号:US06414006B1
公开(公告)日:2002-07-02
申请号:US09416733
申请日:1999-10-13
申请人: Shun-ichi Harada , Gideon A. Rodan , Mohamed Machwate , Marc LaBelle , Kathleen Metters , Robert N. Young
发明人: Shun-ichi Harada , Gideon A. Rodan , Mohamed Machwate , Marc LaBelle , Kathleen Metters , Robert N. Young
IPC分类号: A61K3141
CPC分类号: G01N33/88 , A61K31/00 , A61K31/4196 , A61K31/66 , A61K31/663 , A61K45/06 , G01N2500/04 , G01N2500/10 , A61K2300/00
摘要: The present invention relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype antagonist.
摘要翻译: 本发明涉及用于抑制哺乳动物骨吸收的方法,包括向有需要的哺乳动物施用治疗有效量的EP4受体亚型拮抗剂。
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公开(公告)号:US06586457B2
公开(公告)日:2003-07-01
申请号:US09817424
申请日:2001-03-26
申请人: Shun-Ichi Harada , Mohamed MacHwate , Gideon A. Rodan , Marc Labelle , Kathleen Metters , Robert N. Young
发明人: Shun-Ichi Harada , Mohamed MacHwate , Gideon A. Rodan , Marc Labelle , Kathleen Metters , Robert N. Young
IPC分类号: A61K3141
CPC分类号: G01N33/88 , A61K31/00 , A61K31/4196 , A61K31/66 , A61K31/663 , A61K45/06 , G01N2500/04 , G01N2500/10 , A61K2300/00
摘要: The present invention relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype antagonist.
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公开(公告)号:US5939322A
公开(公告)日:1999-08-17
申请号:US646248
申请日:1996-05-14
IPC分类号: C07D307/68 , C07K14/72 , C12N15/12 , C07K14/705 , C12N15/63 , C12N15/85
CPC分类号: C07K14/721 , C07D307/68 , C07K2319/00
摘要: Through the use of the novel receptor NER in a screening procedure, TOFA (5-tetradecyloxy)-2-furan-carboxylic acid) has been found to modulate other receptors and to be a potent potentiator of other drugs. TOFA activates the NER receptor. The NER receptor is a novel member of the steroid hormone receptor family and has been prepared by cDNA cloning from a human osteosarcoma SAOS-2/B10 cell library. Also disclosed is the complete sequence of human NER cDNA; a COS stable expression system; the expressed NER protein; and an assay using the COS expression system. In addition, the invention relates to a method for identifying functional ligands of the NER receptor.
摘要翻译: PCT No.PCT / US95 / 13924 Sec。 371日期:1996年5月14日 102(e)日期1996年5月14日PCT提交1995年10月24日PCT公布。 第WO96 / 13519号公报 日期1996年5月9日通过在筛选程序中使用新型受体NER,已经发现TOFA(5-十四烷氧基)-2-呋喃羧酸)调节其他受体并成为其他药物的有效增强剂。 TOFA激活NER受体。 NER受体是类固醇激素受体家族的新成员,并通过人骨肉瘤SAOS-2 / B10细胞库的cDNA克隆制备。 还公开了人NER cDNA的完整序列; COS稳定表达系统; 表达的NER蛋白; 和使用COS表达系统的测定法。 另外本发明涉及一种鉴定NER受体功能性配体的方法。
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8.
公开(公告)号:US5856186A
公开(公告)日:1999-01-05
申请号:US862556
申请日:1997-05-23
IPC分类号: C07K14/745 , C12N5/02 , C12N5/078 , G01N33/50 , C12N5/00
CPC分类号: C07K14/745 , C12N5/0643 , G01N33/5008 , G01N33/502 , G01N33/5044 , G01N33/5088 , C12N2502/1311 , C12N2503/02
摘要: Methods of obtaining enriched populations of osteoclast precursor cells which can be released from tissue culture dishes and used for biochemical studies are described. Osteoblastic cells and bone marrow cells are co-cultured. Next a .alpha..sub.v .beta..sub.3 receptor ligand, such as echistatin is used for cell detachment. The result is an 75-95% pure enriched population of tartrate resistant acid phosphatase (TRAP.sup.+) cells, in high yields (2-3.times.10.sup.6 cells per experiment) can be obtained. These cells are mostly mononucleated and based on their characteristics are considered to be pre-fusion osteoclasts (pOC cells). The precursor osteoclasts can be reseeded onto osteoblasts to obtain an enriched population of mature, multinucleated osteoclast cells.
摘要翻译: 描述了可以从组织培养皿中释放并用于生物化学研究的获得富含破骨细胞前体细胞群体的方法。 共培养成骨细胞和骨髓细胞。 接下来,使用αvβ3受体配体,例如echistatin用于细胞分离。 结果是可以获得高产率(每个实验2-3×10 6个细胞)的75-95%纯度富含酒石酸盐酸性磷酸酶(TRAP +)细胞的富集群体。 这些细胞大多是单核的,并且基于其特征被认为是融合前的破骨细胞(pOC细胞)。 前体破骨细胞可以重新种植在成骨细胞上,以获得成熟的多核破骨细胞的富集群体。
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公开(公告)号:US06416964B2
公开(公告)日:2002-07-09
申请号:US09238536
申请日:1999-01-27
申请人: Alfred A. Reszka , Gideon A. Rodan
发明人: Alfred A. Reszka , Gideon A. Rodan
IPC分类号: C12Q148
CPC分类号: G01N33/502 , A61K31/663 , C12Q1/485 , G01N33/5008 , G01N33/5044 , G01N2500/00
摘要: The present invention relates to methods of identifying compounds useful as modulators of certain stress responsive kinases. More particularly, the compounds so identified are useful for treating or preventing diseases or conditions that are mediated by, for example, abnormal bone resorption or angiogenesis. These compounds are useful for treating or preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, and tumor growth.
摘要翻译: 本发明涉及鉴定可用作某些应激反应性激酶调节剂的化合物的方法。 更具体地,如此鉴定的化合物可用于治疗或预防由例如异常骨吸收或血管发生介导的疾病或病症。 这些化合物可用于治疗或预防骨质疏松,抑制血管再狭窄,糖尿病性视网膜病变,黄斑变性,血管生成,动脉粥样硬化,炎症和肿瘤生长。
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10.
公开(公告)号:US6043026A
公开(公告)日:2000-03-28
申请号:US71211
申请日:1998-05-01
IPC分类号: A61K31/445 , A61K31/565 , A61K31/57 , A61K47/48 , C12Q1/00 , A61K51/00
CPC分类号: A61K31/445 , A61K31/565 , A61K31/57 , A61K47/48276
摘要: The combination of an estrogen receptor modulator and a growth hormone secretagogue is useful in the treatment or prevention of diseases involving bone resorption, especially osteoporosis.
摘要翻译: 雌激素受体调节剂和生长激素促分泌素的组合可用于治疗或预防涉及骨吸收,特别是骨质疏松症的疾病。
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