Design and development of biological response modifiers
生物反应调节剂的设计和开发
基本信息
- 批准号:14103018
- 负责人:
- 金额:$ 72.72万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (S)
- 财政年份:2002
- 资助国家:日本
- 起止时间:2002 至 2006
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Various biological response modifiers, including nuclear receptor ligands (agonists/antagonists) and enzyme inhibitors, were designed and prepared, aiming development of agents for the treatment of chronic diseases (cancers, diabetes, rheumatoid diseases etc). Methodologically, functional regulation hypothesis of nuclear receptors based on the lingand-dependent conformational change of their substructure, helix 12, and multi-template hypothesis have been proposed. Based on these hypotheses,(1)ligands (agonists and antagonists) of nuclear receptors [retinoic acid receptors (RARs), retinoid X receptors (RXRs), androgen receptor, progesterone receptor, estrogen receptor, peroxisome proliferators-activated receptors (PPARs), farnsoid X receptor (FXR), liver X receptors (LXRs), and viamine D receptor,(2)specfic and potent inhibitors of tumor necrosis factor (TNF)-α production, tubulin polymerization, puromycin-sensitive aminopeptidase (PSA), α-glucosidase, dipeptidylpeptidase (DPP) type IV, … More tumor cell invasion, histone deacetylase (HDAC), heparanase, calcineulin, cyclooxygenase (COX), nitrogen oxidase synthase (NOS), μ-calpain, thymidine phosphorylase, and angiogenesis, have been created.Typical compounds created in this research project includes;(a)a synthetic retinoid, Am80 (tamibarotene), which has been launched since 2005 as a medicament for the treatment of acute promyelocytic leukemia, and is now under phase II clinical trial for the treatment of Crohn's diseases,(b)a synthetic retinoid, TAC-101, which is now under phase III clinical trial for the treatment of liver cancer,(c)non-steroidal/non-anilide type structure of androgen antagonists which are active toward so-called anti-androgen-resistant cells (ex.LNCaP cells) bearing point mutated androgen receptor(s),(d)novel vitamin D antagonists (DLAMs) containing a nitrogen atom in their structure,(e)steroid hormone receptor ligands containing a carborane group in their structure.Our studies suggests the wide utility/applicability of the above-mentioned hypothesis for drug design, and the usefulness of thalidomide-related phthalimide/homophtalimide skeleton and diphenylpentane structure as the scaffold of various biologically active compounds and steroid-related active compounds, respectively. Less
设计并制备了各种生物反应调节剂,包括核受体配体(激动剂/拮抗剂)和酶抑制剂,旨在开发用于治疗慢性疾病(癌症、糖尿病、类风湿性疾病等)的药剂。在方法论上,提出了核受体的功能调控假说,即基于其亚结构螺旋12构象变化的Lingand依赖性假说和多模板假说。基于这些假设,(1)配体核受体[视黄酸受体(RAR)、类视黄酸X受体(RXR)、雄激素受体、孕酮受体、雌激素受体、过氧化物酶体增殖物激活受体(PPARs)、类法恩索X受体(FXR)、肝X受体(LXR)和维生素D受体]的(激动剂和拮抗剂),(2)肿瘤坏死因子(TNF)-α产生的特异性和有效抑制剂,微管蛋白聚合、嘌呤霉素敏感性氨肽酶(PSA)、α-葡糖苷酶、二肽基肽酶(DPP)IV型, ...更多信息 肿瘤细胞侵袭、组蛋白脱乙酰酶(HDAC)、乙酰肝素酶、钙调神经蛋白、环氧合酶(考克斯)、氮氧化酶合酶(NOS)、μ-钙蛋白酶、胸苷磷酸化酶和血管生成。(a)合成类视色素,Am 80(他米巴罗汀),其自2005年以来作为治疗急性早幼粒细胞白血病的药物上市,并且现在处于用于治疗克罗恩病的II期临床试验中,(B)合成类视色素TAC-101,其现在处于用于治疗肝癌的III期临床试验中,(c)对所谓的抗雄激素抗性细胞有活性的雄激素拮抗剂的非甾体/非苯胺型结构(d)在其结构中含有氮原子的新型维生素D拮抗剂(DLAM),(e)在其结构中含有碳硼烷基团的类固醇激素受体配体。我们的研究表明上述假说对于药物设计的广泛用途/适用性,以及沙利度胺相关的邻苯二甲酰亚胺/高邻苯二甲酰亚胺骨架和二苯基戊烷结构分别作为各种生物活性化合物和类固醇相关活性化合物的支架的有用性。少
项目成果
期刊论文数量(30)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Potent androgen antagonists based on carborane as a hydrophobic core structure
- DOI:10.1021/jm050115j
- 发表时间:2005-07-14
- 期刊:
- 影响因子:7.3
- 作者:Fujii, S;Goto, T;Endo, Y
- 通讯作者:Endo, Y
Anti-angiogenic activity of basic-type, selective cyclooxygenase (COX)-1 inhibitors.
- DOI:10.1016/j.bmcl.2006.02.021
- 发表时间:2006-06
- 期刊:
- 影响因子:2.7
- 作者:H. Sano;T. Noguchi;A. Miyajima;Y. Hashimoto;H. Miyachi
- 通讯作者:H. Sano;T. Noguchi;A. Miyajima;Y. Hashimoto;H. Miyachi
Nuclear receptor antagonists designed based on the helix-folding inhibition hypothesis
- DOI:10.1016/j.bmc.2005.03.027
- 发表时间:2005-09-01
- 期刊:
- 影响因子:3.5
- 作者:Hashimoto, Y;Miyachi, H
- 通讯作者:Miyachi, H
Design, synthesis, and evaluation of a novel series of α-subsituted phenylpropanoic acid derivatives as human peroxisome proliferators-activated receptor (PPAR) α/δ dual agonists for the treatment of metabolic syndrome.
设计、合成和评估一系列新型 α-取代苯丙酸衍生物,作为人过氧化物酶体增殖物激活受体 (PPAR) α/δ 双激动剂,用于治疗代谢综合征。
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Jun-ichi Kasuga;他7名
- 通讯作者:他7名
Evaluation of series of isobenzofuranone dimmers as PKCα ligands : implication for the distance between the two ligand binding sites.
作为 PKCα 配体的一系列异苯并呋喃酮二聚体的评估:两个配体结合位点之间距离的影响。
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:T.Yamaguchi;S.Tashiro;M.Tominaga;M.Kawano;T.Ozeki;M.Fujita;M.Miyauchi;Yoshiyasu Baba 他7名
- 通讯作者:Yoshiyasu Baba 他7名
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HASHIMOTO Yuichi其他文献
HASHIMOTO Yuichi的其他文献
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{{ truncateString('HASHIMOTO Yuichi', 18)}}的其他基金
Development of silicon-containing units as expanded bioisosters
开发含硅单元作为扩展的生物电子等排体
- 批准号:
16K15137 - 财政年份:2016
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Chemical biology of trafficking regulation of membrane cholesterol transporter protein
膜胆固醇转运蛋白运输调节的化学生物学
- 批准号:
25670052 - 财政年份:2013
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
A geographical study of the winter season evacuation in time of disaster in the cold and heavy snow cities using a geo-micro data
基于地微观数据的寒大雪城市冬季灾时疏散地理学研究
- 批准号:
24520883 - 财政年份:2012
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Chemical control of protein dramatype
蛋白质剧型的化学控制
- 批准号:
22249006 - 财政年份:2010
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Protein Knockdown Approach : Hybrid Small Molecules which Induce Proteasome Degradation of Target Proteins
蛋白质击倒方法:诱导目标蛋白质蛋白酶体降解的混合小分子
- 批准号:
21651092 - 财政年份:2009
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Biological response modification based on multi-template and dramatype approaches.
基于多模板和戏剧类型方法的生物反应修改。
- 批准号:
19390028 - 财政年份:2007
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Historical Research on Modern China's Cultural Media from the period of Kantoshu down to the period of Manchuguo.
关东至满洲时期中国近代文化媒介历史研究
- 批准号:
18720083 - 财政年份:2006
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Estblishment of curative therapy for Alzheimer's disease with Humanin peptides
护脑肽治疗阿尔茨海默病的方法的建立
- 批准号:
18590106 - 财政年份:2006
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of anti-tumor agents based on biological response modification.
基于生物反应修饰的抗肿瘤药物的开发。
- 批准号:
17016013 - 财政年份:2005
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Establishment of curative therapy for Alzheimer's disease with Humanin peptides
护脑肽治疗阿尔茨海默病的建立
- 批准号:
16590088 - 财政年份:2004
- 资助金额:
$ 72.72万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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