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An in vivo screen for biological and chemical regulators of mammalial PDEs

An in vivo screen for biological and chemical regulators of mammalial PDEs
哺乳动物 PDE 生物和化学调节剂的体内筛选
批准号:
7337165
负责人:
CHARLES S. HOFFMAN
金额:
$19.43万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
已结题
起止时间:
2007-01-01 至 2009-06-30

项目摘要

项目成果

CHARLES S. HOFFMAN的其他基金

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中文摘要
翻译
许多生物过程是由细胞感知环境中的分子并创造的能力来调节的
英文摘要
Many biological processes are regulated by a cell's ability to sense molecules in its environment and create an intracellular signal to effect an appropriate biological response. One major signaling pathway involves the regulation of cAMP levels, which is a function of cAMP synthesis by adenylate cyclases and cAMP destruction by cAMP phosphodiesterases (PDE). In the fission yeast, Schizosaccharomyces pombe, cAMP levels are regulated by a glucose signaling pathway that includes a single PDE gene. We have developed reporter constructs,which confer growth phenotypes that reflect the cell's intracellular cAMP level. We propose to introduce mammalian PDE genes into our strains, such that the growth behavior will be a function of PDE activity. We will use such strains to carry out the following two aims. 1) We will conduct high throughput screening for chemical inhibitors of specific PDEs. Utilizing strains expressing various murine PDEs (4A, 4B, 8A, 8B), we expect to identify both nonspecific and specific inhibitors. Of note, there are no known PDE8-specific inhibitors, thus making it difficult to determine the relative role of PDES enzymes in various biological processes. 2) We will use these strains to screen a cDNA library for biological activatorsof the target PDE and identify the tissues in which these activatorsare expressed. Strains expressing both the activator and the target PDE will be subjected to chemical library screens for compounds that inhibit the activator, rather than the PDE itself. As these activators may be expressed in a subset of tissues in which the PDE is found, compounds that target the activator may provide a more tissue-specific effect on PDE activity, and thus provide a therapeutic benefit with less of a side-effect than would be possible for compounds that target the PDE directly. There is a broad range of diseases that are currently being treated with PDE inhibitors, or are thought to be amenable to treatment with PDE inhibitors. Therefore, the development of this in vivo platform to identify chemical and biological regulators of PDEs has the potential of identifying the next generation of PDE-related Pharmaceuticalsfor the treatment of cardiac, pulmonary, and renal diseases, as well as certain cancers, cystic fibrosis, multiple sclerosis, rheumatoid arthritis, Huntington's Disease, allergic rhinitis, psoriasis, schizophrenia, Alzheimer's disease and depression.
期刊论文(10)
专著(0)
科研奖励(0)
会议论文
DOI: 10.3389/fphar.2021.833156
发表时间: 2021
期刊: Frontiers in pharmacology
影响因子: 5.6
作者: [Hoffman CS]
通讯作者: Hoffman CS
DOI: 10.1371/journal.pone.0071279
发表时间: 2013
期刊: PloS one
影响因子: 3.7
作者: [Demirbas D, Wyman AR, Shimizu-Albergine M, Cakici O, Beavo JA, Hoffman CS]
通讯作者: Hoffman CS
Fission yeast-based high-throughput screens for PKA pathway inhibitors and activators.
基于裂变酵母的 PKA 途径抑制剂和激活剂高通量筛选。
DOI: 10.1007/978-1-4939-2269-7_6
发表时间: 2015
期刊: Methods in molecular biology (Clifton, N.J.)
影响因子: --
作者: [deMedeiros,AnaSantos, Kwak,Grace, Vanderhooft,Jordan, Rivera,Sam, Gottlieb,Rachel, Hoffman,CharlesS]
通讯作者: Hoffman,CharlesS
DOI: 10.1177/1087057110362100
发表时间: 2010-04
期刊: Journal of biomolecular screening
影响因子: --
作者: [Alaamery MA, Wyman AR, Ivey FD, Allain C, Demirbas D, Wang L, Ceyhan O, Hoffman CS]
通讯作者: Hoffman CS
Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders
  • 批准号:
    10260396
  • 项目类别:
  • 资助金额:
    $73.78万
  • 财政年份:
    2020
  • 负责人:
    CHARLES S. HOFFMAN
  • 依托单位:
Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders
  • 批准号:
    10617261
  • 项目类别:
  • 资助金额:
    $72.6万
  • 财政年份:
    2020
  • 负责人:
    CHARLES S. HOFFMAN
  • 依托单位:
Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders
  • 批准号:
    10401488
  • 项目类别:
  • 资助金额:
    $73.15万
  • 财政年份:
    2020
  • 负责人:
    CHARLES S. HOFFMAN
  • 依托单位:
ADENYLATE CYCLASE-ASSOCIATED COMPLEXES IN SCHIZOSACCHAROMYCES POMBE
  • 批准号:
    7602230
  • 项目类别:
  • 资助金额:
    $0.62万
  • 财政年份:
    2007
  • 负责人:
    CHARLES S. HOFFMAN
  • 依托单位:
海外基金