Abstract
In this paper, we report comprehensive experimental and chemoinformatics analyses of the solubility of small organic molecules (“fragments”) in dimethyl sulfoxide (DMSO) in the context of their ability to be tested in screening experiments. Here, DMSO solubility of 939 fragments has been measured experimentally using an NMR technique. A Support Vector Classification model was built on the obtained data using the ISIDA fragment descriptors. The analysis revealed 34 outliers: experimental issues were retrospectively identified for 28 of them. The updated model performs well in 5-fold cross-validation (balanced accuracy = 0.78). The datasets are available on the Zenodo platform (DOI:10.5281/zenodo.4767511) and the model is available on the website of the Laboratory of Chemoinformatics.
Highlights
Screening methods have become indisputably an integral part of the drug discovery process [1,2], from hit identification to the evaluation of pharmacological properties
In this paper, we report comprehensive experimental and chemoinformatics analyses of the solubility of small organic molecules (“fragments”) in dimethyl sulfoxide (DMSO) in the context of their ability to be tested in screening experiments
Over the past decades fragment-based screening (FBS) has gained a broad acceptance as an efficient alternative to the conventional high-throughput screening (HTS) [2,3]. This is related to the core idea of FBS, which involves analysis of relatively small libraries containing simple yet diverse organic scaffolds, or fragments, and the identification of hit fragments, that will be developed into more potent lead compounds
Summary
Screening methods have become indisputably an integral part of the drug discovery process [1,2], from hit identification to the evaluation of pharmacological properties. Over the past decades fragment-based screening (FBS) has gained a broad acceptance as an efficient alternative to the conventional high-throughput screening (HTS) [2,3] This is related to the core idea of FBS, which involves analysis of relatively small libraries containing simple yet diverse organic scaffolds, or fragments, and the identification of hit fragments, that will be developed into more potent lead compounds. Low solubility directly affects the availability of a compound in solution, which may potentially lead to masking of its actual activity This is notably important for compounds in FBS libraries since the typical concentration of samples is around 1 mM [8,9,10]. One of the solvents commonly used in screening methods is dimethyl sulfoxide (DMSO), a well-established standard [12]
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