Ace Therapeutics specializes in H. pylori research and provides drug development services targeting the pH-responsive regulation system of H. pylori to kill H. pylori by destroying H. pylori colonization.
The human stomach is an unstable environment with a wide pH range, and H. pylori have adapted to the human stomach environment and developed a system to regulate its gene expression according to the pH of the stomach. This system is known as the ArsRS two-component system (TCS). The system regulates the expression of over 170 H. pylori genes, including genes important for acid adaptation (urease, amidase), genes for oxidative stress, genes for membrane proteins, and transcriptional regulatory genes related to iron or nickel homeostasis.
Fig. 1 Pie charts showing putative functions of 178 differentially expressed genes regulated by the ArsRS TCS (Loh et al. 2020).
ArsRS TCS is an important contributor to the adaptive survival of H. pylori in the stomach and we conduct in-depth studies on this regulatory system. Now, we provide small molecule drug development services targeting the key enzymes in it. One is ArsS, the other one is ArsR.
ArsS is the sensor of the system and it is a histidine kinase. We offer to design small molecule drugs based on its histidine kinase property. We offer to block its autophosphorylation by designing small molecule drugs to cut off the perception of its histidine protonation, thus cutting off its reception of acid signals. In addition, we also offer to design small molecule drugs targeting its site of action with ArsR to block its transmission to acid signaling.
ArsR is the response regulator of the system and it is trans-phosphorylated by auto-phosphorylated ArsS. Based on this, we offer to design small molecule drugs targeting its site of action with ArsS to block the acid signaling. As trans-phosphorylated ArsR has a better DNA-binding affinity toward an amount of acid-responsive gene promoters, we help to design small molecule drugs targeting its site of action with DNA. What's more, as there are essential genes that a non-phosphorylated form of ArsR can regulate, we offer to design small molecule drugs targeting the non-phosphorylated form of ArsS. We comprehensively consider the structure and active site of ArsR with a view to discovering small molecule drugs targeting both non-phosphorylated and phosphorylated forms of ArsS.
Contact us
Ace Therapeutics has extensive development experience in small molecule drugs for the treatment of H. pylori, and we help develop highly effective drugs for the treatment of H. pylori based on a thorough understanding of the various molecules of H. pylori. The ArsRS TCS is a key factor in the survival and customization of H. pylori in the stomach, and we offer small molecule drug development services targeting two key enzymes in this system (AsrS and AsrR). If you share our goals, please contact us for co-development!
References
- Loh, J. T.; et al. Delineation of the pH-responsive regulon controlled by the Helicobacter pylori ArsRS two-component system. Infection and Immunity. 2021, 89(4): e00597-20.
- González, A.; et al. Small molecule inhibitors of the response regulator ArsR exhibit bactericidal activity against Helicobacter pylori. Microorganisms. 2020, 8(4): 503.
※ All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
