APJ receptor agonism for metabolic syndrome

APJ 受体激动剂治疗代谢综合征

基本信息

  • 批准号:
    9899980
  • 负责人:
  • 金额:
    $ 48.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-04-01 至 2022-03-31
  • 项目状态:
    已结题

项目摘要

The overall goal of this project is to develop apelin (APJ) receptor agonists to treat diet-induced obesity (DIO) and related metabolic syndrome. Metabolic syndrome can lead to several life threatening conditions including hypertension, heart disease, type II diabetes, steatohepatitis, stroke, and certain types of cancer. Available medications to treat obesity have serious side effects and limited efficacy. Thus, new medications around novel targets are needed. The APJ receptor is a G-protein coupled receptor (GPCR) protein that is activated by apelin peptides and a newly described hormone called TODDLER/ELABELA. It is an emerging multi-modal target for metabolic syndrome that needs pharmacological validation. Apelin is an insulin sensitizer that promotes fatty acid oxidation. Apelin knockout (ko) mice have higher insulin levels and glucose intolerance along with increased abdominal fat and higher bodyweight. Apelin through its interaction with APJ can inhibit maturation of pre-adipocytes and lipolysis in mature adipocytes. Activation of APJ by apelin in the endothelium leads to the formation of large, non-leaky lymphatic and blood vessels that restrict the transport of FA and their uptake in adipose. In agreement with these data, apelin ko mice have vessels that are more amenable to FA transport. Another report has indicated that apelin transgenic mice are resistant to DIO by virtue of increased vascular mass and mitochondrial biogenesis in skeletal muscles. Non-peptide probes of this receptor suitable for in vivo work are not available. We have identified a structurally novel agonist scaffold for further development through high-throughput screening. We propose to refine our early lead compounds to produce in vivo probes of APJ using three iterative specific aims. Through aim 1, synthesis and refinement of APJ probes will continue using medicinal chemistry approaches. Through aim 2, these compounds will be characterized using functional and radioligand displacement assays for APJ. Potent compounds will be then characterized using a battery of ADMET and pharmacokinetic assays. Through aim 3, in vivo testing of the best compounds will be performed in a chronic model of DIO in rodents. Completion of the project will pharmacologically validate APJ as a target for medications development to treat metabolic syndrome and produce advanced lead compounds for eventual clinical development.
本项目的总体目标是开发APJ受体激动剂治疗饮食性肥胖

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

RANGAN MAITRA其他文献

RANGAN MAITRA的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('RANGAN MAITRA', 18)}}的其他基金

Conduct Confirmatory and Specialized In Vitro Testing and Screening of Interventional Agents in Standard Formats
以标准格式对介入药物进行验证性和专门的体外测试和筛选
  • 批准号:
    10925108
  • 财政年份:
    2023
  • 资助金额:
    $ 48.62万
  • 项目类别:
Conduct In Vitro Screening of Interventional Agents in High Throughput Screening (HTS) Formats: High Throughput Screening to Identify HIV Inhibitors
以高通量筛选 (HTS) 形式对介入药物进行体外筛选:通过高通量筛选识别 HIV 抑制剂
  • 批准号:
    10925107
  • 财政年份:
    2023
  • 资助金额:
    $ 48.62万
  • 项目类别:
Preclinical Services for HIV Therapeutics: QA/QC Plan and Task Order Initiation Meeting
HIV 治疗的临床前服务:QA/QC 计划和任务订单启动会议
  • 批准号:
    10397451
  • 财政年份:
    2021
  • 资助金额:
    $ 48.62万
  • 项目类别:
Novel therapeutic approach for NASH
NASH 的新治疗方法
  • 批准号:
    10426164
  • 财政年份:
    2020
  • 资助金额:
    $ 48.62万
  • 项目类别:
Novel therapeutic approach for NASH
NASH 的新治疗方法
  • 批准号:
    10179374
  • 财政年份:
    2020
  • 资助金额:
    $ 48.62万
  • 项目类别:
Novel therapeutic approach for NASH
NASH 的新治疗方法
  • 批准号:
    10616609
  • 财政年份:
    2020
  • 资助金额:
    $ 48.62万
  • 项目类别:
APJ receptor agonism for metabolic syndrome
APJ 受体激动剂治疗代谢综合征
  • 批准号:
    9239698
  • 财政年份:
    2017
  • 资助金额:
    $ 48.62万
  • 项目类别:
Investigation of Synthetic Cannabinoid Exposures and Pharmacological Consequences
合成大麻素暴露和药理学后果的调查
  • 批准号:
    10521643
  • 财政年份:
    2016
  • 资助金额:
    $ 48.62万
  • 项目类别:
Investigation of Synthetic Cannabinoid Exposures and Pharmacological Consequences
合成大麻素暴露和药理学后果的调查
  • 批准号:
    10704595
  • 财政年份:
    2016
  • 资助金额:
    $ 48.62万
  • 项目类别:
In vivo probes for the APJ receptor.
APJ 受体的体内探针。
  • 批准号:
    9095375
  • 财政年份:
    2014
  • 资助金额:
    $ 48.62万
  • 项目类别:

相似国自然基金

相似海外基金

Recruitment of brown adipocytes in visceral white adipose tissue by fibroblast growth factor 8b
成纤维细胞生长因子 8b 将棕色脂肪细胞募集到内脏白色脂肪组织中
  • 批准号:
    321208980
  • 财政年份:
    2016
  • 资助金额:
    $ 48.62万
  • 项目类别:
    Research Grants
Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8827438
  • 财政年份:
    2014
  • 资助金额:
    $ 48.62万
  • 项目类别:
Induction of brown-like adipocytes in white adipose tissue by food-derived factors
食物源性因子在白色脂肪组织中诱导棕色样脂肪细胞
  • 批准号:
    26450168
  • 财政年份:
    2014
  • 资助金额:
    $ 48.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
WAT-on-a-chip - Development of a micofluidic, microphysiologic in vitro adipose tissue model for high-throughput drug screening based on hiPSC-derived adipocytes.
WAT-on-a-chip - 开发微流体、微生理体外脂肪组织模型,用于基于 hiPSC 衍生脂肪细胞的高通量药物筛选。
  • 批准号:
    257256526
  • 财政年份:
    2014
  • 资助金额:
    $ 48.62万
  • 项目类别:
    Research Fellowships
Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8828181
  • 财政年份:
    2013
  • 资助金额:
    $ 48.62万
  • 项目类别:
Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8520690
  • 财政年份:
    2013
  • 资助金额:
    $ 48.62万
  • 项目类别:
Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8629741
  • 财政年份:
    2013
  • 资助金额:
    $ 48.62万
  • 项目类别:
Effect of exercise training on formation of brite adipocytes within white adipose tissue
运动训练对白色脂肪组织内脂肪细胞形成的影响
  • 批准号:
    23700778
  • 财政年份:
    2011
  • 资助金额:
    $ 48.62万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Investigation for the mechanisms of the emergence of brown adipocytes in white adipose tissue
白色脂肪组织中棕色脂肪细胞出现机制的研究
  • 批准号:
    21780261
  • 财政年份:
    2009
  • 资助金额:
    $ 48.62万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
LOUISIANA COBRE: P1: INDUCE THERMOGENIC BROWN ADIPOCYTES IN WHITE ADIPOSE TISSUE
路易斯安那 COBRE:P1:在白色脂肪组织中诱导产热棕色脂肪细胞
  • 批准号:
    7610781
  • 财政年份:
    2007
  • 资助金额:
    $ 48.62万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了