New ACE2 activator and its prodrug as novel therapeutic reagents for inflammatory pulmonary diseases

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Principal Investigator: Hongpeng  Jia
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2021
Award: $204,688
Funding agency: National Institute of Allergy and Infectious Diseases

Project title: New ACE2 activator and its prodrug as novel therapeutic reagents for
inflammatory pulmonary diseases.
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.

Terms: <0-11 years old><ACE2><Agonist><Angiotensin Converting Enzyme><Angiotensin I-Converting Enzyme><Applications Grants><Bacterial Pneumonia><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood Pressure><Buffers><CD143 Antigens><Carboxycathepsin><Cause of Death><Cell Communication and Signaling><Cell Signaling><Child><Child Youth><Children (0-21)><Development><Dipeptidyl Peptidase A><Disease><Disorder><Drug Precursors><Drugs><Elderly><Gene Targeting><Goals><Grant Proposals><Host Defense><Impairment><Inflammation><Inflammatory><Inflammatory Response><Intracellular Communication and Signaling><Kininase A><Kininase II><Lung><Lung Inflammation><Lung Respiratory System><Lung damage><Lung diseases><Marrow Neutrophil><Medical><Medication><Methodology><Mice><Mice Mammals><Molecular><Morbidity><Morbidity - disease rate><Murine><Mus><Names><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Organoids><Patients><Peptidyl-Dipeptidase A><Pharmaceutic Preparations><Pharmaceutical Preparations><Pharmacology><Physiologic><Physiological><Pneumonia><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Pro-Drugs><Prodrugs><Public Health><Pulmonary Diseases><Pulmonary Disorder><Reagent><Receptor Protein><Regulation><Renin-Angiotensin System><Research><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><Signal Pathway><Signal Transduction><Signal Transduction Systems><Signaling><Source><Specificity><System><Testing><Therapeutic><Validation><advanced age><angiotensin converting enzyme 2><angiotensin converting enzyme II><arm><bacteria pneumonia><base><biological signal transduction><chemical library><clinical relevance><clinically relevant><developmental><disease of the lung><disorder of the lung><drug/agent><efficacy analysis><efficacy assessment><efficacy evaluation><efficacy examination><elders><evaluate efficacy><examine efficacy><geriatric><inflammatory lung disease><insight><late life><later life><lung disorder><lung injury><mortality><mouse model><murine model><neutrophil><new drug treatments><new drugs><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapeutics><new therapy><new therapy approaches><next generation therapeutics><novel><novel drug treatments><novel drugs><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapeutics><novel therapy><novel therapy approach><older adult><older person><pneumonia model><pneumonia models><pre-clinical><preclinical><prevent><preventing><pulmonary><receptor><senior citizen><sex><small molecule><small molecule libraries><tool><youngster>