Supplement to "New ACE2 activator and its prodrug as novel therapeutic regents for inflammatory pulmonary diseases"

“新型 ACE2 激活剂及其前药作为炎症性肺部疾病的新型治疗药物”的补充

• 批准号: 10265687
• 负责人: Hongpeng Jia
• 金额: $ 20.21万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-02 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265687
• 关键词: ACE2; Agonist; Applications Grants; Bacterial Pneumonia; Blood Pressure; Buffers; Cause of Death; Child; Development; Disease; Elderly; Gene Targeting; Goals; Host Defense; Impairment; Inflammation; Inflammatory; Inflammatory Response; Lung; Lung Inflammation; Lung diseases; Medical; Methodology; Molecular; Morbidity - disease rate; Mus; Names; Organoids; Patients; Peptidyl-Dipeptidase A; Pharmaceutical Preparations; Pharmacology; Physiological; Pneumonia; Prodrugs; Public Health; Reagent; Regulation; Renin-Angiotensin System; Research; Signal Pathway; Signal Transduction; Source; Specificity; System; Testing; Therapeutic; Validation; arm; base; clinically relevant; efficacy evaluation; inflammatory lung disease; insight; lung injury; mortality; mouse model; neutrophil; novel; novel therapeutic intervention; novel therapeutics; pneumonia model; pre-clinical; prevent; receptor; sex; small molecule; small molecule libraries; tool

Summary of the Funded Parent Grant (1R21AI149321-01, 01/01/2020 - 12/31/2021) Pneumonia and associated inflammatory lung diseases (ILD) are a leading cause of death among children and elderly worldwide and a significant source of morbidity and mortality among hospitalized patients. Interestingly, the diseases are associate with over-activation of the renin-angiotensin system and impaired ACE2 activity. The overall goal of present study will validate the therapeutic benefits of a newly discovered class of ACE2 activators, named H4, in bacterial pneumonia associated inflammatory lung disease. The immediate objectives of this application are: 1) To explore the mechanisms by which H4 and its prodrugs buffer RAS over-activity; 2) To evaluate the efficacy of and strategies for H4 and its prodrugs to reverse the development of bacterial pneumonia by limiting neutrophilic lung inflammation. This project is highly significant because ILD are associated with many infectious and non-infectious lung diseases, in which, many of them are projected to remain the leading cause of death. Therefore, not only our research will lead to the validation of a new therapy but we will assess the impact of that treatment for inflammatory lung diseases. These studies will make a significant pre-clinical insight of a novel ACE2 activator, h4 and its pro- drug in preventing and treating inflammatory lung diseases.

已资助的家长补助金摘要（1 R21 AI 149321 -01，01/01/2020 - 12/31/2021） 肺炎和相关的炎性肺病（ILD）是儿童死亡的主要原因 和老年人，是住院患者发病率和死亡率的重要来源。 有趣的是，这些疾病与肾素-血管紧张素系统的过度激活和受损有关。 ACE 2活性。本研究的总体目标是验证新发现的 在细菌性肺炎相关的炎性肺病中，这类ACE 2激活剂，命名为H4。 本申请的直接目标是：1）探索H4及其 前药缓冲RAS过度活性; 2）评估H4及其前药的功效和策略， 通过限制嗜酸性肺部炎症逆转细菌性肺炎的发展。 由于ILD与许多感染性和非感染性肺疾病相关，因此该项目具有高度意义 疾病，其中许多疾病预计仍将是导致死亡的主要原因。因此，不仅我们 研究将导致一种新疗法的验证，但我们将评估这种治疗的影响， 炎症性肺病 这些研究将对新型ACE 2激活剂h4及其前体进行重要的临床前研究。 预防和治疗炎症性肺病的药物。