Host cell signalling inhibitors against helicobacter pylori

More than 50% of the world population is infected by Helicobacter pylori nowdays. Although in most cases it doesn't causes any symptoms it's a significant risk factor in the development of gastric ulcer or gastric carcinoma. Elimination of the bacteria can be attained by the combination of at least three drugs and it may also causes several side effects. It's beyond doubt that a new drug showing good efficacy without side effects is needed. Kinase inhibitors have proved their usefulness in the treatment of cancer inhibiting cell proliferation via inhibition of intracellular signaling system. Moreover host cell kinases can be involved in viral or bacterial infections, this way human kinases may be the targets of the treatment. In our research we are investigating kinase inhibitors and developing novel compounds for host cell inhibition. The point of our strategy (called chemistry driven drug development) is to identify active compounds in cellular assay and identify cellular targets afterwards. Initially, we are using the Nested Chemical Library™ (NCL) technology for hit finding and lead optimization. Core of the NCL is Chemical Validation Library (CVL) which can be used for hit finding in the preliminary screen. 313 compounds of CVL were tested and focused libraries were prepared around the validated hit molecules of the first screen. After three optimization cycle lead compounds were identified. From one of the best lead compounds we have prepared a special derivative containing a linker which can be used to attach to an affinity column for target fishing in chemistry driven drug development. Target fishing is an efficient proteomic method in seeking cellular drug targets based on affinity chromatography, 2D electrophoresis and MS-MS protein identification.