20.500.12556/RUL-138679 Screening of big pharma’s library against various in-house biological targets Open innovation initiatives provide opportunities for collaboration and sharing of knowledge and experience between industry, academia, and government institutions. Through open innovation, Merck is offering a Mini Library of 80 carefully selected compounds from previous research and development projects to a broader scientific community for testing in academic drug discovery projects. These compounds are predominantly drug-like and cover a broad range of molecular targets. They could potentially interact with other enzymes, receptors, transporters, and ion channels of interest. The Mini Library was tested on seven in-house enzymes (bacterial MurA, MurC ligase, and DdlB enzyme, human MAO-A/B, human BChE, and murine AChE), and several hits were identified. A follow-up series of structural analogues provided by Merck gave a more detailed insight into the accessibility and the quality of the hit compounds. For example, sartan derivatives were moderate inhibitors of MurC, whereas bisarylureas were potent, selective, nanomolar inhibitors of hMAO-B. Importantly, 3-n-butyl-substituted indoles were identified as low nanomolar selective inhibitors of hBChE. All in all, the hit derivatives provide new starting points for the further exploration of the chemical space of high-quality enzyme inhibitors. Merck Mini Library screening MurA MurC human MAO-A/B human BChE murine AchE Merckova mini knjižnica pregledovanje humani MAO-A/B humani BChE mišji AchE true false true Angleški jezik Slovenski jezik Neznano 2022-08-09 11:30:46 2022-08-09 11:30:58 2022-09-15 04:17:03 0000-00-00 00:00:00 2022 0 0 12 str. iss. 14, art. 4484 Vol. 27 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2022-08-13 615.4:54 1420-3049 10.3390/molecules27144484 117586947 https://www.mdpi.com/1420-3049/27/14/4484 1 b029433c-17c5-11ed-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=159074 molecules-27-04484-v2.pdf molecules-27-04484-v2.pdf 1 8C682560C0DAFEFC65F01DC190D65854 4d3e19b91e50c3f5782fbbaea820880dc4b47311e64ca7eb0016a4f16d1c2db6 d17cb898-17c6-11ed-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=159075 Fakulteta za farmacijo 0 0 0