LFA-9 (mPGES-1/5-LOX Inhibitor): Preclinical Studies to Support a Clinical Trial,

LFA-9(mPGES-1/5-LOX 抑制剂):支持临床试验的临床前研究,

基本信息

  • 批准号:
    10794912
  • 负责人:
  • 金额:
    $ 41.87万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-17 至 2024-03-16
  • 项目状态:
    已结题

项目摘要

Familial Adenomatous Polyposis (FAP) is a rare inherited disease which results from an autosomal dominant genetic alteration in the adenomatous polyposis coli (APC) gene. Patients with this disease develop hundreds to thousands of pre-cancerous polyps (adenomas) in the duodenum, colon and rectum. Left untreated, patients have almost 100% lifetime risk of developing colorectal cancer (CRC). There is unequivocal evidence of chemopreventive efficacy in CRC with anti-inflammatory agents that exert their effects through COX-2 inhibition (e.g. aspirin, ibuprofen, naproxen and celecoxib), however chronic use of these agents is associated with an increased risk of GI toxicity. Moreover, agents that target COX-2 have been implicated in cardiovascular (CV) and thrombotic events for patients with a baseline history of atherosclerotic heart disease. Several investigators have shown the increased CV risk to be associated with reduced levels of prostaglandin I2 (PGI2 or prostacyclin) and increased levels of 5-lipoxygenase (5-LOX) metabolites. Hence, Dr. Rao and others hypothesize that agents that spare PGI2 and selectively block production of prostaglandin E-2 (PGE2) and 5-LOX metabolites should prove promising in the prevention of CRC. One such agent, licofelone, targets microsomal prostaglandin E Synthase-1 (mPGES-1) and 5-LOX, and suppresses small intestinal and colonic tumor formation in the ApcMin/+ mouse at doses that are devoid of overt toxicity. Inhibition of intestinal tumors was also associated with decreases in inflammatory cytokines and COX and 5-LOX activities. Furthermore, in clinical trials for OA, the common side effects with licofelone were mild (abdominal pain and diarrhea). In silico molecular docking techniques and in vitro and in vivo screening methods have been employed to identify biologically active licofelone analogs. The lead candidate of this effort, LFA- 9, has been selected for further development. The main objective of this Task Order RFP is to conduct preclinical studies with LFA-9 to support its use in a clinical trial.
家族性腺瘤性息肉病(FAP)是一种罕见的遗传性疾病,由大肠腺瘤性息肉病(APC)基因的常染色体显性遗传改变引起。患有这种疾病的患者在十二指肠、结肠和直肠中会出现成百上千的癌前息肉(腺瘤)。如果不及时治疗,患者一生中患结直肠癌(CRC)的风险几乎为100%。

项目成果

期刊论文数量(0)
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科研奖励数量(0)
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专利数量(0)

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David McCormick其他文献

David McCormick的其他文献

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{{ truncateString('David McCormick', 18)}}的其他基金

Brain States and Flexible Behavior
大脑状态和灵活行为
  • 批准号:
    10700739
  • 财政年份:
    2020
  • 资助金额:
    $ 41.87万
  • 项目类别:
LFA-9 (mPGES-1/5-LOX Inhibitor): Preclinical Studies to Support a Clinical Trial,
LFA-9(mPGES-1/5-LOX 抑制剂):支持临床试验的临床前研究,
  • 批准号:
    10399397
  • 财政年份:
    2018
  • 资助金额:
    $ 41.87万
  • 项目类别:
IGF::OT::IGF NExT Preclinical Toxicology & Pharmacology of Drugs Developed for Cancer Patients, TO#3, Exploratory Studies of CCR4 CART Cells
IGF::OT::IGF NExT 临床前毒理学
  • 批准号:
    10361380
  • 财政年份:
    2017
  • 资助金额:
    $ 41.87万
  • 项目类别:
Mechanisms of Rapid Modulation of Auditory Responsiveness
听觉反应快速调节机制
  • 批准号:
    10055961
  • 财政年份:
    2016
  • 资助金额:
    $ 41.87万
  • 项目类别:
Cortical Dynamics and Neural/Behavioral Performance
皮质动力学和神经/行为表现
  • 批准号:
    10544429
  • 财政年份:
    2016
  • 资助金额:
    $ 41.87万
  • 项目类别:
Cortical Dynamics and Neural/Behavioral Performance
皮质动力学和神经/行为表现
  • 批准号:
    10530597
  • 财政年份:
    2016
  • 资助金额:
    $ 41.87万
  • 项目类别:
Cortical Dynamics and Neural/Behavioral Performance
皮质动力学和神经/行为表现
  • 批准号:
    10058278
  • 财政年份:
    2016
  • 资助金额:
    $ 41.87万
  • 项目类别:
Cortical Dynamics and Neural/Behavioral Performance
皮质动力学和神经/行为表现
  • 批准号:
    10304870
  • 财政年份:
    2016
  • 资助金额:
    $ 41.87万
  • 项目类别:
CALCIUM SIGNALING AND PREFRONTAL DEFICITS IN SCHIZOPHRENIA
精神分裂症的钙信号传导和前额叶缺陷
  • 批准号:
    7958212
  • 财政年份:
    2009
  • 资助金额:
    $ 41.87万
  • 项目类别:
Properties of Axons and Synaptic Communication in the Neocortex
新皮质中轴突和突触通讯的特性
  • 批准号:
    7760193
  • 财政年份:
    2008
  • 资助金额:
    $ 41.87万
  • 项目类别:

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患有功能性腹痛疾病的青少年的睡眠结构被破坏
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    22K16013
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针对有功能性腹痛风险的幼儿进行基于互联网的预防干预的随机对照试验
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