Deep learning enables rapid identification of potent DDR1 kinase inhibitors.
basic_science · Level V
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- Record sourced from PubMed, PMID 31477924.
- Also identified by DOI 10.1038/s41587-019-0224-x.
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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.
Medical subject headings
- Deep Learning
- Discoidin Domain Receptor 1
- Drug Evaluation, Preclinical