Deep learning enables rapid identification of potent DDR1 kinase inhibitors.
Nat Biotechnol
; 37(9): 1038-1040, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-31477924
ABSTRACT
We have developed a deep generative model, generative tensorial reinforcement learning (GENTRL), for de novo small-molecule design. GENTRL optimizes synthetic feasibility, novelty, and biological activity. We used GENTRL to discover potent inhibitors of discoidin domain receptor 1 (DDR1), a kinase target implicated in fibrosis and other diseases, in 21 days. Four compounds were active in biochemical assays, and two were validated in cell-based assays. One lead candidate was tested and demonstrated favorable pharmacokinetics in mice.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Evaluación Preclínica de Medicamentos
/
Receptor con Dominio Discoidina 1
/
Aprendizaje Profundo
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Biotechnol
Asunto de la revista:
BIOTECNOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Hong Kong