doi: 10.1038/s41587-019-0224-x. Epub 2019 Sep 2.
Deep learning enables rapid identification of potent DDR1 kinase inhibitors
Alex Zhavoronkov 1, Yan A Ivanenkov 2, Alex Aliper 2, Mark S Veselov 2, Vladimir A Aladinskiy 2, Anastasiya V Aladinskaya 2, Victor A Terentiev 2, Daniil A Polykovskiy 2, Maksim D Kuznetsov 2, Arip Asadulaev 2, Yury Volkov 2, Artem Zholus 2, Rim R Shayakhmetov 2, Alexander Zhebrak 2, Lidiya I Minaeva 2, Bogdan A Zagribelnyy 2, Lennart H Lee 3, Richard Soll 3, David Madge 3, Li Xing 3, Tao Guo 3, Alán Aspuru-Guzik 4 5 6 7
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- PMID:31477924
- DOI: 10.1038/s41587-019-0224-x
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Deep learning enables rapid identification of potent DDR1 kinase inhibitors
Alex Zhavoronkov et al. Nat Biotechnol.2019 Sep.
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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.
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- Has Drug Design Augmented by Artificial Intelligence Become a Reality?Chen H, Engkvist O.Chen H, et al.Trends Pharmacol Sci. 2019 Nov;40(11):806-809. doi: 10.1016/j.tips.2019.09.004. Epub 2019 Oct 16.Trends Pharmacol Sci. 2019.PMID:31629547
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