Heterocyclic inhibitors of qcrb as novel drugs for infections caused by nontuberculous mycobacteria
Active Project Grant Awarded Last action
- Award ID
- R43AI188991
- Recipient
-
Fimbrion Therapeutics Inc. UEI N9RQX3G4EH54
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $600,002
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 65% complete
- Place of performance
- St. Louis, MO 63108, USA
Award details come from USAspending.gov.
Description
- Abstract
- Non-tuberculosis mycobacteria (NTM) are a diverse group of environmental bacteria and opportunistic pathogens capable of causing numerous human infections, the most common of which is NTM pulmonary disease (NTM-PD). The most clinically relevant pathogens causing NTM-PD are members of the mycobacterium abscessus complex (MAB) and the mycobacterium avium complex (MAC). NTM-PD is especially problematic in immunosuppressed patients or those with lung conditions such as cystic fibrosis or chronic obstructive pulmonary disease, dramatically worsening the prognosis of such patients. Many NTM, including MAB and MAC, are intrinsically resistant to antibiotics, making the treatment of NTM-PD exceptionally difficult. Currently recommended therapeutic courses require the administration of ≥3 antibiotics for at least 12- 18 months. This intensive treatment frequently leads to drug induced toxicity and the potential for adverse drug-drug interactions while resulting in NTM clearance in only 34-67% of cases caused by drug susceptible NTM and 11-21% of cases caused by drug resistant NTM, with rates of relapse or recurrence ranging from 25- 49% in "cured" individuals. Therefore, new and safe drugs, with novel mechanisms of action are desperately needed to effectively treat NTM-PD by reducing treatment time, preventing relapse/recurrence and improving clinical outcomes, with reduced drug-induced adverse events. Fimbrion is developing a small molecule series that targets the mycobacterium tuberculosis (MTB) respiratory protein qcrb. We have made substantial progress optimizing the drug-like properties of our qcrb inhibitors, which display low-nanomolar potency against MTB, possess good drug-like properties, have excellent in vivo oral pharmacokinetic (PK) profiles (high oral bioavailability and low intrinsic clearance) and show little-to-no eukaryotic cytotoxicity (CC50), with typical safety indices (SI) CC50/IC50 >1000. As qcrb is conserved between MTB and the ntms, we tested 30 of our qcrbmtb inhibitors against representative strains of the MAB and MAC and identified several compounds with good anti-MAB activity (IC50
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $300,001 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Original award | $300,001 |
Quick answers
Who received award R43AI188991?
R43AI188991 was awarded to Fimbrion Therapeutics Inc. by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 23, 2025.
How much is award R43AI188991 worth?
$600,002 has been obligated on R43AI188991.
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