KinomeMETA: meta-learning enhanced kinome-wide polypharmacology profiling.
Brief Bioinform
; 25(1)2023 11 22.
Article
em En
| MEDLINE
| ID: mdl-38113075
ABSTRACT
Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polifarmacologia
/
Antineoplásicos
Idioma:
En
Revista:
Brief Bioinform
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China