20.500.12556/RUL-143239 Fragment-sized thiazoles in fragment-based drug discovery campaigns friend or foe? Thiazoles exhibit a wide range of biological activities and therefore represent useful and attractive building blocks. To evaluate their usefulness and pinpoint their liabilities in fragment screening campaigns, we assembled a focused library of 49 fragment-sized thiazoles and thiadiazoles with various substituents, namely amines, bromides, carboxylic acids, and nitriles. The library was profiled in a cascade of biochemical inhibition assays, redox activity, thiol reactivity, and stability assays. Our study indicates that when thiazole derivatives are identified as screening hits, their reactivity should be carefully addressed and correlated with specific on-target engagement. Importantly, nonspecific inhibition should be excluded using experimental approaches and in silico predictions. To help with validation of hits identified in fragment screening campaigns, we can apply our high-throughput profiling workflow to focus on the most tractable compounds with a clear mechanism of action. thiazoles hit profiling promiscuous compounds frequent hitters privileged scaffolds fragments hit profiliranje promiskuitetne spojine pogosti napadalci privilegirani odri fragmenti tiazoli farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2022-12-09 07:50:53 2022-12-09 07:50:55 2023-02-16 03:41:11 0000-00-00 00:00:00 2022 0 0 Str. 1905–1910 iss. 12 Vol. 13 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 547.78:615.4:54 1948-5875 10.1021/acsmedchemlett.2c00429 130706947 acsmedchemlett.2c00429.pdf acsmedchemlett.2c00429.pdf 1 E86DBB9F5C097394033A065F612F3404 b29be38abdd1612509f74d5736c47857040f284b21e4075c07094f099755d2f7 6273a314-ad10-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=166601 https://pubs.acs.org/doi/10.1021/acsmedchemlett.2c00429 1 ab49ee01-778d-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=164859 Fakulteta za farmacijo 0 0 0