Optimized chemogenomic library design strategies for precision oncology
| Autor: | Timothy Johanssen, Daniel Ebner, Balaguru Ravikumar, Paschalis Athanasiadis, Tero Aittokallio, Paul A. Clemons, Neil O. Carragher |
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| Rok vydání: | 2020 |
| Předmět: |
Library design
0303 health sciences Cellular activity genetic structures Phenotypic screening Small Molecule Libraries Computational biology medicine.disease behavioral disciplines and activities Small molecule 3. Good health 03 medical and health sciences 0302 clinical medicine nervous system Precision oncology 030220 oncology & carcinogenesis Chemical diversity medicine psychological phenomena and processes 030304 developmental biology Glioblastoma |
| Popis: | Designing a focused compound screening library of bioactive small molecules is a challenging task since many compounds modulate their effects through multiple protein targets with various degrees of potency and selectivity. We describe here several analytic procedures with adjustable cut-off parameters that enable one to design anticancer target-focused compound libraries optimized for library size, cellular activity, biological and chemical diversity and target selectivity. Even though our focus was on designing compound libraries to enable a comprehensive investigation of the target biology of glioblastoma (GBM), the compound collections cover a wide range of protein targets and biological pathways implicated in various types of cancers, making the libraries widely applicable in precision oncology studies. We published the final screening set library, called the Comprehensive anti-Cancer small-Compound Library, or C3L.We hope these general library design principles and the current, widely annotated small molecule libraries will prove useful for the community in various phenotypic screening experiments in GBM and other cancers. |
| Databáze: | OpenAIRE |
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