地址1
盘状结构域
计算生物学
激酶
新颖性
生物
受体酪氨酸激酶
鉴定(生物学)
药理学
生物化学
植物
神学
哲学
作者
Alex Zhavoronkov,Yan A. Ivanenkov,Alex Aliper,Mark S. Veselov,Vladimir Aladinskiy,Anastasiya V Aladinskaya,Victor A Terentiev,Daniil Polykovskiy,M. S. Kuznetsov,Arip Asadulaev,Yury Volkov,Artem Zholus,Rim Shayakhmetov,Alexander Zhebrak,Lidiya I. Minaeva,Bogdan Zagribelnyy,Lennart H Lee,Richard Söll,David S. Madge,Xing Li,Tao Guo,Alán Aspuru‐Guzik
标识
DOI:10.1038/s41587-019-0224-x
摘要
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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