Cargando…

A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases

In the field of rare and intractable diseases, new drug development is difficult and drug repositioning (DR) is a key method to improve this situation. In this study, we present a new method for finding DR candidates utilizing virtual screening, which integrates amino acid interaction mapping into s...

Descripción completa

Detalles Bibliográficos
Autores principales: Tanabe, Mao, Sakate, Ryuichi, Nakabayashi, Jun, Tsumura, Kyosuke, Ohira, Shino, Iwato, Kaoru, Kimura, Tomonori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632405/
https://www.ncbi.nlm.nih.gov/pubmed/37938624
http://dx.doi.org/10.1038/s41598-023-46648-1
_version_ 1785132569085345792
author Tanabe, Mao
Sakate, Ryuichi
Nakabayashi, Jun
Tsumura, Kyosuke
Ohira, Shino
Iwato, Kaoru
Kimura, Tomonori
author_facet Tanabe, Mao
Sakate, Ryuichi
Nakabayashi, Jun
Tsumura, Kyosuke
Ohira, Shino
Iwato, Kaoru
Kimura, Tomonori
author_sort Tanabe, Mao
collection PubMed
description In the field of rare and intractable diseases, new drug development is difficult and drug repositioning (DR) is a key method to improve this situation. In this study, we present a new method for finding DR candidates utilizing virtual screening, which integrates amino acid interaction mapping into scaffold-hopping (AI-AAM). At first, we used a spleen associated tyrosine kinase inhibitor as a reference to evaluate the technique, and succeeded in scaffold-hopping maintaining the pharmacological activity. Then we applied this method to five drugs and obtained 144 compounds with diverse structures. Among these, 31 compounds were known to target the same proteins as their reference compounds and 113 compounds were known to target different proteins. We found that AI-AAM dominantly selected functionally similar compounds; thus, these selected compounds may represent improved alternatives to their reference compounds. Moreover, the latter compounds were presumed to bind to the targets of their references as well. This new “compound-target” information provided DR candidates that could be utilized for future drug development.
format Online
Article
Text
id pubmed-10632405
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-106324052023-11-10 A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases Tanabe, Mao Sakate, Ryuichi Nakabayashi, Jun Tsumura, Kyosuke Ohira, Shino Iwato, Kaoru Kimura, Tomonori Sci Rep Article In the field of rare and intractable diseases, new drug development is difficult and drug repositioning (DR) is a key method to improve this situation. In this study, we present a new method for finding DR candidates utilizing virtual screening, which integrates amino acid interaction mapping into scaffold-hopping (AI-AAM). At first, we used a spleen associated tyrosine kinase inhibitor as a reference to evaluate the technique, and succeeded in scaffold-hopping maintaining the pharmacological activity. Then we applied this method to five drugs and obtained 144 compounds with diverse structures. Among these, 31 compounds were known to target the same proteins as their reference compounds and 113 compounds were known to target different proteins. We found that AI-AAM dominantly selected functionally similar compounds; thus, these selected compounds may represent improved alternatives to their reference compounds. Moreover, the latter compounds were presumed to bind to the targets of their references as well. This new “compound-target” information provided DR candidates that could be utilized for future drug development. Nature Publishing Group UK 2023-11-08 /pmc/articles/PMC10632405/ /pubmed/37938624 http://dx.doi.org/10.1038/s41598-023-46648-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tanabe, Mao
Sakate, Ryuichi
Nakabayashi, Jun
Tsumura, Kyosuke
Ohira, Shino
Iwato, Kaoru
Kimura, Tomonori
A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases
title A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases
title_full A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases
title_fullStr A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases
title_full_unstemmed A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases
title_short A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases
title_sort novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632405/
https://www.ncbi.nlm.nih.gov/pubmed/37938624
http://dx.doi.org/10.1038/s41598-023-46648-1
work_keys_str_mv AT tanabemao anovelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT sakateryuichi anovelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT nakabayashijun anovelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT tsumurakyosuke anovelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT ohirashino anovelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT iwatokaoru anovelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT kimuratomonori anovelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT tanabemao novelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT sakateryuichi novelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT nakabayashijun novelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT tsumurakyosuke novelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT ohirashino novelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT iwatokaoru novelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases
AT kimuratomonori novelinsilicoscaffoldhoppingmethodfordrugrepositioninginrareandintractablediseases