HpgGT Inhibitors as Novel Antiinfectives


The emergence of antibiotic resistance and cross-resistance is challenging medical care as well as pharmaceutical industry. However, the medical need is hardly met by the development of novel antibiotic substances, of which only few have been approved in the recent years. The aim of this project is to develop novel small molecule inhibitors against important bacterial targets as highly selective antiinfective agents. This approach aims to reduce side effects as well as cross resistance. The inhibitors are directed against bacterial proteins (virulence factors) which are essential for establishment of the infection.

Gamma-glutamyltransferase (GGT) plays a key role in drug and xenobiotic detoxification through glutathione metabolism. Although bacterial and mammalian GGT share considerable sequence homology, structural variations
in the active site allow for the design of small-molecule inhibitors selective for certain bacterial GGTs like the Helicobacter pylori GGT (HpGT). Helicobacter pylori with a lack of GGT exhibit a considerably reduced growth rate, what renders GGT to an attractive target for the invention of new antibacterial drugs.


HpgGT Inhibitor Program

Target: Helicobacter pylori-gamma-Glutamyltranspeptidase (HpgGT)

  • Functional target class: HpgGT is central for establishing and maintaining H. pylori immune evasion via impacting T-cell activation, proliferation and effector functions
  • Goal: development of small molecule HpgGT/glutathione interaction antagonist
  • Therapeutic area: Immunomodulation
  • Indication: prevention of gastric ulcers and cancers
  • Mode of administration: oral
  • Hit finding supported by PriaXplore®: preliminary candidate with good in-vitro potency and selectivity