The metabolism of organisms is vitally important for survival. Ace Therapeutics provides drug development services targeting enzymes related to the energy metabolism of H. pylori to help block energy metabolism to kill H. pylori.
H. pylori lives in microaerobic conditions and genes of enzymes related to the glycolytic pathway and tricarboxylic acid cycle (TCA cycle) have been shown to be present in the DNA of H. pylori. Based on the microaerobic metabolic profile of H. pylori, two important enzymes affecting the aerobic metabolism of H. pylori are found. One is flavodoxin and the other is pyruvate ferredoxin oxidoreductase (PFOR). Both enzymes are essential for the survival of H. pylori. And compounds that interfere with this pathway can be helpful for H. pylori eradication.
Fig. 1 Aerobic metabolism of H. pylori.
Ace Therapeutics offers drug development services targeting H. pylori flavodoxin and PFOR to help kill H. pylori by disrupting H. pylori metabolism.
Drug development targeting H. pylori flavodoxin
The absence of flavodoxin in human cells is a prerequisite for our drug development services against flavodoxin. We develop small molecule drugs based on three properties of H. pylori flavodoxin.
1. H. pylori flavodoxin is a small acidic redox protein.
2. Flavin mononucleotide is a cofactor of H. pylori flavodoxin, and flavin mononucleotide binds tightly to flavodoxin.
3. H. pylori flavodoxin has a unique pocket structure just near the active site.
Among them, the third property is the most important property of H. pylori flavodoxin. The unique pocket distinguishes H. pylori flavodoxin from other bacterial flavodoxin and from the flavodoxin-like domain in human cytochrome P450 reductase. And we focus on developing small molecule drugs targeting this unique pocket.
Drug development targeting PFOR
The PFOR of H. pylori is directly related to the energy metabolism of H. pylori and is an ideal target for H. pylori therapy. We provide small molecule drug development services for H. pylori PFOR and explore it in the following 3 directions.
1. Bismuth, which is widely used for the treatment of H. pylori, can down-regulate the expression of the alpha subunit of H. pylori PFOR. We help explore small molecule drugs that can regulate the expression of PFOR protein like bismuth.
2. The missense mutation of PFOR in H. pylori makes H. pylori resistant to nitrofurans. We offer to explore small molecule drugs similar to thiamine pyrophosphate (PFOR cofactor) to avoid the effect of missense mutation.
3. We offer to explore small-molecule inhibitors targeting the functional structural domains of H. pylori PFOR.
Contact us
Ace Therapeutics has an in-depth insight into the energy metabolism of H. pylori and provides drug development services for key enzymes in its metabolism. We provide drug development services not only for flavodoxin and PFOR but also for other metabolic enzymes, including 2-oxoglutarate-acceptor oxidoreductase subunit D, flavodoxin quinone reductase, and fumarate reductase. Please contact us for specialized drug development services targeting the energy metabolism of H. pylori.
References
- Salillas, S.; et al. Design, synthesis, and efficacy testing of nitroethylene- and 7-nitrobenzoxadiazol-based flavodoxin inhibitors against Helicobacter pylori drug-resistant clinical strains and in Helicobacter pylori-infected mice. Journal of Medicinal Chemistry. 2019, 62(13): 6102-15.
- Steiner, T. M.; et al. Substrate usage determines carbon flux via the citrate cycle in Helicobacter pylori. Molecular Microbiology. 2021, 116(3): 841-60.
- Yao, X.; et al. Integrative proteomic and metabolomic analyses reveal the mechanism by which bismuth enables Helicobacter pylori eradication. Helicobacter. 2021, 26(6): e12846.
※ All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
