R01AI170765
Project Grant
Overview
Grant Description
Targeting NUOD for the treatment of H. pylori - This proposal aims to develop novel, more effective, and selective therapies for the treatment of Helicobacter pylori infections. Chronic infection with H. pylori causes peptic ulcers and gastric cancer. H. pylori is an important drug-resistant pathogen, which is categorized as a high-priority pathogen by the WHO.
Standard therapy consists of a proton pump inhibitor (PPI) and two broad-spectrum antibiotics, usually clarithromycin with either metronidazole or amoxicillin. These combinations are becoming increasingly ineffective with high resistance rates and substantially disrupt the gut's healthy microbiome. There is a considerable unmet need for novel, more effective, and selective antibiotics to eradicate H. pylori.
In our preliminary studies, we identified the NUOD interface of Complex I as a druggable target for H. pylori. Respiration through Complex I is essential for H. pylori, but not for most other bacteria, offering mechanistic selectivity and minimizing disruption of the microbiome. We developed and validated a virtual screening platform for this target to identify leads with improved pharmacological properties using the initial inhibitors.
The virtual screen identified hits that are synthetically tractable with demonstrated on-target antibacterial activity, and both ex vivo and in vivo efficacy against H. pylori. The ultimate aim of the proposal is to obtain carefully validated, narrow spectrum, orally bioavailable, and efficacious NUOD inhibitors that will form the basis of a subsequent preclinical antibiotic development effort.
These studies will also provide a deeper understanding of H. pylori respiration and the development of selective antibiotics against H. pylori.
Standard therapy consists of a proton pump inhibitor (PPI) and two broad-spectrum antibiotics, usually clarithromycin with either metronidazole or amoxicillin. These combinations are becoming increasingly ineffective with high resistance rates and substantially disrupt the gut's healthy microbiome. There is a considerable unmet need for novel, more effective, and selective antibiotics to eradicate H. pylori.
In our preliminary studies, we identified the NUOD interface of Complex I as a druggable target for H. pylori. Respiration through Complex I is essential for H. pylori, but not for most other bacteria, offering mechanistic selectivity and minimizing disruption of the microbiome. We developed and validated a virtual screening platform for this target to identify leads with improved pharmacological properties using the initial inhibitors.
The virtual screen identified hits that are synthetically tractable with demonstrated on-target antibacterial activity, and both ex vivo and in vivo efficacy against H. pylori. The ultimate aim of the proposal is to obtain carefully validated, narrow spectrum, orally bioavailable, and efficacious NUOD inhibitors that will form the basis of a subsequent preclinical antibiotic development effort.
These studies will also provide a deeper understanding of H. pylori respiration and the development of selective antibiotics against H. pylori.
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Memphis,
Tennessee
38105
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 293% from $865,480 to $3,400,420.
St. Jude Children's Research Hospital was awarded
NUOD Inhibitors: Novel Antibiotics for H. pylori Eradication
Project Grant R01AI170765
worth $3,400,420
from the National Institute of Allergy and Infectious Diseases in May 2023 with work to be completed primarily in Memphis Tennessee United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.855 Allergy and Infectious Diseases Research.
The Project Grant was awarded through grant opportunity NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 5/21/26
Period of Performance
5/1/23
Start Date
4/30/28
End Date
Funding Split
$3.4M
Federal Obligation
$0.0
Non-Federal Obligation
$3.4M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for R01AI170765
Transaction History
Modifications to R01AI170765
Additional Detail
Award ID FAIN
R01AI170765
SAI Number
R01AI170765-3895287343
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Nonprofit With 501(c)(3) IRS Status (Other Than An Institution Of Higher Education)
Awarding Office
75NM00 NIH National Institute of Allergy and Infectious Diseases
Funding Office
75NM00 NIH National Institute of Allergy and Infectious Diseases
Awardee UEI
JL4JHE9SDRR3
Awardee CAGE
0L0C5
Performance District
TN-09
Senators
Marsha Blackburn
Bill Hagerty
Bill Hagerty
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute of Allergy and Infectious Diseases, National Institutes of Health, Health and Human Services (075-0885) | Health research and training | Grants, subsidies, and contributions (41.0) | $865,480 | 100% |
Modified: 5/21/26