Novel Modulators of HDL Metabolism

HDL 代谢的新型调节剂

基本信息

  • 批准号:
    7744773
  • 负责人:
  • 金额:
    $ 27.05万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-09-01 至 2011-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular disease remains the leading cause of morbidity and mortality for both men and women, accounting for nearly 40% of annual deaths. High levels of low-density lipoprotein cholesterol (LDL-C) and low level of high-density lipoprotein cholesterol (HDL-C) are well-known risk factors for heart disease. Although lowering LDL-C levels using a number of marketed drugs, of which statins are the leading drugs, has significantly reduced coronary artery disease, substantial residual cardiovascular risk remains, even with very aggressive reductions in levels of LDL-C. Accordingly, attention is now shifting toward strategies for targeting HDL as adjunctive therapy to prevent and treat cardiovascular disease. Many studies have emphasized that the risk factor associated with low level of HDL is independent of that of high LDL-C. Recent epidemiological data confirmed that patients with low HDL-C level are at high risk of premature cardiovascular disease no matter how low the LDL level. These and other patients will dramatically benefit from an aggressive treatment of low HDL-C. The long-term goal of this work is to develop novel drugs for increasing HDL-C. Our therapeutic target is endothelial lipase (EL), a member of the lipoprotein lipase gene family that hydrolyzes HDL phospholipids. Recent studies demonstrated that inhibition of EL in mice results in a significant increase in HDL-C levels. To achieve our goal, we have established a sensitive assay to screen for inhibitors of human EL, and we have identified screening hits. As part of this Phase I proposal, we plan to screen for additional hits, develop SAR for all our hits, and confirm the ability of the selected compounds to increase the HDL-C level using in situ and in vivo assays. PUBLIC HEALTH RELEVANCE: Project Narrative Heart disease is the leading cause of death for both men and women in the US. A high blood cholesterol level is a well-known risk factor for heart disease. There are two types of cholesterol in the blood, bad cholesterol (LDL) and good cholesterol (HDL). To lower the risk of heart disease, LDL levels should be lowered and HDL should be raised. Although bad cholesterol can be lowered using a number of marketed drugs, these drugs do not treat a large segment of the population with low HDL levels. Our goal is to develop new drugs that raise the levels of good cholesterol as a means of decreasing the risk of heart disease.
描述(由申请人提供):心血管疾病仍然是男性和女性发病和死亡的主要原因,占每年死亡人数的近40%。高水平的低密度脂蛋白胆固醇(LDL-C)和低水平的高密度脂蛋白胆固醇(HDL-C)是众所周知的心脏病危险因素。尽管使用许多市售药物(其中他汀类药物是主要药物)降低LDL-C水平已显著降低冠状动脉疾病,但即使LDL-C水平非常积极地降低,仍存在大量残余心血管风险。因此,注意力现在转向靶向HDL作为预防和治疗心血管疾病的连续疗法的策略。许多研究强调低HDL水平的危险因素与高LDL-C水平无关。最近的流行病学资料证实,无论LDL水平如何低,HDL-C水平低的患者都是早发心血管疾病的高危人群。这些患者和其他患者将从低HDL-C的积极治疗中获益。这项工作的长期目标是开发增加HDL-C的新药。我们的治疗目标是内皮脂肪酶(EL),脂蛋白脂肪酶基因家族的成员,水解HDL磷脂。最近的研究表明,抑制小鼠EL会导致HDL-C水平显着升高。为了实现我们的目标,我们已经建立了一个敏感的检测方法来筛选人EL的抑制剂,我们已经确定了筛选命中。作为第一阶段提案的一部分,我们计划筛选更多的命中,为我们所有的命中开发SAR,并使用原位和体内试验确认所选化合物增加HDL-C水平的能力。公共卫生相关性:项目叙述心脏病是美国男性和女性的主要死亡原因。高胆固醇水平是众所周知的心脏病风险因素。血液中有两种胆固醇:坏胆固醇(LDL)和好胆固醇(HDL)。为了降低患心脏病的风险,应降低LDL水平,升高HDL水平。虽然坏胆固醇可以降低使用一些上市的药物,这些药物不治疗低HDL水平的人群的一大部分。我们的目标是开发提高有益胆固醇水平的新药,以降低心脏病的风险。

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(1)

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Nabil A Elshourbagy其他文献

Renal ATP Citrate Lyase (ATP CL) Protein Localizes throughout the Nephron and Increases Only in the Proximal Tubule with Chronic Metabolic Acidosis (CMA)
肾型 ATP 柠檬酸裂合酶(ATP CL)蛋白定位于整个肾单位,且仅在慢性代谢性酸中毒(CMA)时在近端小管中增加
  • DOI:
    10.1203/00006450-199904020-01996
  • 发表时间:
    1999-04-01
  • 期刊:
  • 影响因子:
    3.100
  • 作者:
    Krishna Puttaparthi;Thomas Rogers;Nabil A Elshourbagy;Moshe Levi;Joel Z Melnick
  • 通讯作者:
    Joel Z Melnick

Nabil A Elshourbagy的其他文献

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{{ truncateString('Nabil A Elshourbagy', 18)}}的其他基金

Oral PCSK9/LDLR antagonist direction to the clinic
口服 PCSK9/LDLR 拮抗剂临床指导
  • 批准号:
    9906738
  • 财政年份:
    2020
  • 资助金额:
    $ 27.05万
  • 项目类别:
Development of Oral Small Molecule PCSK9 Antagonist
口服小分子PCSK9拮抗剂的研制
  • 批准号:
    9346559
  • 财政年份:
    2017
  • 资助金额:
    $ 27.05万
  • 项目类别:
Novel Modulators of HDL Metabolism
HDL 代谢的新型调节剂
  • 批准号:
    8487433
  • 财政年份:
    2009
  • 资助金额:
    $ 27.05万
  • 项目类别:
Novel Modulators of LDL Metabolism
低密度脂蛋白代谢的新型调节剂
  • 批准号:
    8646627
  • 财政年份:
    2009
  • 资助金额:
    $ 27.05万
  • 项目类别:
Novel Modulators of LDL Metabolism
低密度脂蛋白代谢的新型调节剂
  • 批准号:
    7668863
  • 财政年份:
    2009
  • 资助金额:
    $ 27.05万
  • 项目类别:
Novel Modulators of LDL Metabolism
低密度脂蛋白代谢的新型调节剂
  • 批准号:
    7822161
  • 财政年份:
    2009
  • 资助金额:
    $ 27.05万
  • 项目类别:
Novel Modulators of HDL Metabolism
HDL 代谢的新型调节剂
  • 批准号:
    8311108
  • 财政年份:
    2009
  • 资助金额:
    $ 27.05万
  • 项目类别:

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