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Quantitative Estimate Index for Early-Stage Screening of Compounds Targeting Protein-Protein Interactions

Drug-likeness quantification is useful for screening drug candidates. Quantitative estimates of drug-likeness (QED) are commonly used to assess quantitative drug efficacy but are not suitable for screening compounds targeting protein-protein interactions (PPIs), which have recently gained attention....

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Autores principales: Kosugi, Takatsugu, Ohue, Masahito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539639/
https://www.ncbi.nlm.nih.gov/pubmed/34681589
http://dx.doi.org/10.3390/ijms222010925
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author Kosugi, Takatsugu
Ohue, Masahito
author_facet Kosugi, Takatsugu
Ohue, Masahito
author_sort Kosugi, Takatsugu
collection PubMed
description Drug-likeness quantification is useful for screening drug candidates. Quantitative estimates of drug-likeness (QED) are commonly used to assess quantitative drug efficacy but are not suitable for screening compounds targeting protein-protein interactions (PPIs), which have recently gained attention. Therefore, we developed a quantitative estimate index for compounds targeting PPIs (QEPPI), specifically for early-stage screening of PPI-targeting compounds. QEPPI is an extension of the QED method for PPI-targeting drugs that models physicochemical properties based on the information available for drugs/compounds, specifically those reported to act on PPIs. FDA-approved drugs and compounds in iPPI-DB, which comprise PPI inhibitors and stabilizers, were evaluated using QEPPI. The results showed that QEPPI is more suitable than QED for early screening of PPI-targeting compounds. QEPPI was also considered an extended concept of the “Rule-of-Four” (RO4), a PPI inhibitor index. We evaluated the discriminatory performance of QEPPI and RO4 for datasets of PPI-target compounds and FDA-approved drugs using F-score and other indices. The F-scores of RO4 and QEPPI were 0.451 and 0.501, respectively. QEPPI showed better performance and enabled quantification of drug-likeness for early-stage PPI drug discovery. Hence, it can be used as an initial filter to efficiently screen PPI-targeting compounds.
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spelling pubmed-85396392021-10-24 Quantitative Estimate Index for Early-Stage Screening of Compounds Targeting Protein-Protein Interactions Kosugi, Takatsugu Ohue, Masahito Int J Mol Sci Article Drug-likeness quantification is useful for screening drug candidates. Quantitative estimates of drug-likeness (QED) are commonly used to assess quantitative drug efficacy but are not suitable for screening compounds targeting protein-protein interactions (PPIs), which have recently gained attention. Therefore, we developed a quantitative estimate index for compounds targeting PPIs (QEPPI), specifically for early-stage screening of PPI-targeting compounds. QEPPI is an extension of the QED method for PPI-targeting drugs that models physicochemical properties based on the information available for drugs/compounds, specifically those reported to act on PPIs. FDA-approved drugs and compounds in iPPI-DB, which comprise PPI inhibitors and stabilizers, were evaluated using QEPPI. The results showed that QEPPI is more suitable than QED for early screening of PPI-targeting compounds. QEPPI was also considered an extended concept of the “Rule-of-Four” (RO4), a PPI inhibitor index. We evaluated the discriminatory performance of QEPPI and RO4 for datasets of PPI-target compounds and FDA-approved drugs using F-score and other indices. The F-scores of RO4 and QEPPI were 0.451 and 0.501, respectively. QEPPI showed better performance and enabled quantification of drug-likeness for early-stage PPI drug discovery. Hence, it can be used as an initial filter to efficiently screen PPI-targeting compounds. MDPI 2021-10-10 /pmc/articles/PMC8539639/ /pubmed/34681589 http://dx.doi.org/10.3390/ijms222010925 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kosugi, Takatsugu
Ohue, Masahito
Quantitative Estimate Index for Early-Stage Screening of Compounds Targeting Protein-Protein Interactions
title Quantitative Estimate Index for Early-Stage Screening of Compounds Targeting Protein-Protein Interactions
title_full Quantitative Estimate Index for Early-Stage Screening of Compounds Targeting Protein-Protein Interactions
title_fullStr Quantitative Estimate Index for Early-Stage Screening of Compounds Targeting Protein-Protein Interactions
title_full_unstemmed Quantitative Estimate Index for Early-Stage Screening of Compounds Targeting Protein-Protein Interactions
title_short Quantitative Estimate Index for Early-Stage Screening of Compounds Targeting Protein-Protein Interactions
title_sort quantitative estimate index for early-stage screening of compounds targeting protein-protein interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539639/
https://www.ncbi.nlm.nih.gov/pubmed/34681589
http://dx.doi.org/10.3390/ijms222010925
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