TY  - JOUR
AB  - The EUOS/SLAS challenge aimed to facilitate the development of reliable algorithms to predict the aqueous solubility of small molecules using experimental data from 100K compounds. In total, hundred teams took part in the challenge to predict low, medium and highly soluble compounds as measured by the nephelometry assay. This article describes the winning model, which was developed using the publicly available Online CHEmical database and Modeling environment (OCHEM) available on the website https://ochem.eu/article/​​27. We describe in detail the assumptions and steps used to select methods, descriptors and strategy which contributed to the winning solution. In particular we show that consensus based on 28 models calculated using descriptor-based and representation learning methods allowed us to obtain the best score, which was higher than those based on individual approaches or consensus models developed using each individual approach. A combination of diverse models allowed us to decrease both bias and variance of individual models and to calculate the highest score. The model based on Transformer CNN contributed the best individual score thus highlighting the power of Natural Language Processing (NLP) methods. The inclusion of information about aleatoric uncertainty would be important to better understand and use the challenge data by the contestants.
AU  - Hunklinger, A.
AU  - Hartog, P.
AU  - Šícho, M.*
AU  - Godin, G.*
AU  - Tetko, I.V.
C1  - 69878
C2  - 55300
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
TI  - The openOCHEM consensus model is the best-performing open-source predictive model in the First EUOS/SLAS Joint Compound Solubility Challenge.
JO  - SLAS Discov.
VL  - 29
IS  - 2
PB  - Elsevier Science Inc
PY  - 2024
SN  - 2472-5552
ER  - 

TY  - JOUR
AB  - Small-molecule screening is a powerful approach to identify modulators of either specific biological targets or cellular pathways with phenotypic endpoints. A myriad of assay technologies are available to assess the activity of enzymes, monitor protein-protein interactions, measure transcription factor activity in reporter assays, or detect cellular features and activities using high-content imaging. A common challenge during small-molecule screening is, however, the presence of hit compounds generating assay interference, thereby producing false-positive hits. Thus, efforts are needed to uncover such interferences to prioritize high-quality hits for further analysis. This process encompasses (1) computational approaches to flag undesirable compounds, and (2) the use of experimental approaches like counter, orthogonal, and cellular fitness screens to identify and eliminate artifacts. In this brief guide, we provide an overview for first-time users, highlighting experimental screening strategies to prioritize high-quality bioactive hits from high-throughput screening/high-content screening (HTS/HCS) campaigns.
AU  - Rothenaigner, I.
AU  - Hadian, K.
C1  - 61888
C2  - 50504
CY  - 2455 Teller Rd, Thousand Oaks, Ca 91320 Usa
SP  - 851-854
TI  - Brief Guide: Experimental strategies for high-quality hit selection from small-molecule screening campaigns.
JO  - SLAS Discov.
VL  - 26
IS  - 7
PB  - Sage Publications Inc
PY  - 2021
SN  - 2472-5552
ER  - 

TY  - JOUR
AB  - Compound screening in biological assays and subsequent optimization of hits is indispensable for the development of new molecular research tools and drug candidates. To facilitate such discoveries, the European Research Infrastructure EU-OPENSCREEN was founded recently with the support of its member countries and the European Commission. Its distributed character harnesses complementary knowledge, expertise, and instrumentation in the discipline of chemical biology from 20 European partners, and its open working model ensures that academia and industry can readily access EU-OPENSCREEN's compound collection, equipment, and generated data. To demonstrate the power of this collaborative approach, this perspective article highlights recent projects from EU-OPENSCREEN partner institutions. These studies yielded (1) 2-aminoquinazolin-4(3H)-ones as potential lead structures for new antimalarial drugs, (2) a novel lipodepsipeptide specifically inducing apoptosis in cells deficient for the pVHL tumor suppressor, (3) small-molecule-based ROCK inhibitors that induce definitive endoderm formation and can potentially be used for regenerative medicine, (4) potential pharmacological chaperones for inborn errors of metabolism and a familiar form of acute myeloid leukemia (AML), and (5) novel tankyrase inhibitors that entered a lead-to-candidate program. Collectively, these findings highlight the benefits of small-molecule screening, the plethora of assay designs, and the close connection between screening and medicinal chemistry within EU-OPENSCREEN.
AU  - Brennecke, P.*
AU  - Rasina, D.*
AU  - Aubi, O.*
AU  - Herzog, K.*
AU  - Landskron, J.*
AU  - Cautain, B.*
AU  - Vicente, F.*
AU  - Quintana, J.*
AU  - Mestres, J.*
AU  - Stechmann, B.*
AU  - Ellinger, B.*
AU  - Brea, J.*
AU  - Kolanowski, J.L.*
AU  - Pilarski, R.*
AU  - Orzaez, M.*
AU  - Pineda-Lucena, A.*
AU  - Laraia, L.*
AU  - Nami, F.*
AU  - Zielenkiewicz, P.*
AU  - Paruch, K.*
AU  - Hansen, E.*
AU  - von Kries, J.P.*
AU  - Neuenschwander, M.*
AU  - Specker, E.*
AU  - Bartunek, P.*
AU  - Simova, S.*
AU  - Leśnikowski, Z.*
AU  - Krauss, S.*
AU  - Lehtiö, L.*
AU  - Bilitewski, U.*
AU  - Brönstrup, M.*
AU  - Taskén, K.*
AU  - Jirgensons, A.*
AU  - Lickert, H.
AU  - Clausen, M.H.*
AU  - Andersen, J.H.*
AU  - Vicent, M.J.*
AU  - Genilloud, O.*
AU  - Martinez, A.*
AU  - Nazaré, M.*
AU  - Fecke, W.*
AU  - Gribbon, P.*
C1  - 55099
C2  - 46295
CY  - 2455 Teller Rd, Thousand Oaks, Ca 91320 Usa
SP  - 398-413
TI  - EU-OPENSCREEN: A novel collaborative approach to facilitate chemical biology.
JO  - SLAS Discov.
VL  - 24
IS  - 3
PB  - Sage Publications Inc
PY  - 2019
SN  - 2472-5552
ER  -