engleski

New project generation platform combining in silico and in vitro approaches

The purpose of these investigations was to use compounds already in the depository or compounds bank, cluster them into representative set of molecules and then screen on different biological targets. In this way, information on additional qualities of in-house compounds based on interactions with different novel targets was acquired. This research gave an opportunity by which the compound classes arising from different in-house chemistry expertise could be used as a starting point for the new indications. In this way, synthetic chemistry, in vitro screening and computational drug design approaches were synergistically combined to provide added value to compounds already in the depository or compounds bank. To carry out targeted screening, diverse representative set of compounds from compound database were pre-selected by in silico approach. Since there is always a possibility that some interesting compounds may drop out at the very beginning and not be included in the final set to be tested on biological assays, virtual screening was run in parallel, and in this way information about the number of false positives and negatives, that is screening efficiency, was obtained. The obtained results are in accordance within ordinary acceptable limits and the described approach has been considered as a normal “way of performing systematic research activities”. In silico and biological screening were performed on the following therapeutic targets: Dipeptidyl peptidase IV - DPP IV/CD26 ; Hematopoietic Cell Kinase - Hck, Lyn Tyrosine Kinase, Fyn Tyrosine Kinase - p59fyn, ZAP-70 Tyrosine Kinase, and Lck Tyrosine Kinase - p56lck. Initial set-up of the above mentioned approach and some interesting results will be presented.

in silico screening; in vitro screening; druggable targets

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