Generative Network Complex for the Automated Generation of Drug-like Molecules.

Journal of Chemical Information and Modeling
Kaifu GaoGuo-Wei Wei

Abstract

Current drug discovery is expensive and time-consuming. It remains a challenging task to create a wide variety of novel compounds that not only have desirable pharmacological properties but also are cheaply available to low-income people. In this work, we develop a generative network complex (GNC) to generate new drug-like molecules based on the multiproperty optimization via the gradient descent in the latent space of an autoencoder. In our GNC, both multiple chemical properties and similarity scores are optimized to generate drug-like molecules with desired chemical properties. To further validate the reliability of the predictions, these molecules are reevaluated and screened by independent 2D fingerprint-based predictors to come up with a few hundreds of new drug candidates. As a demonstration, we apply our GNC to generate a large number of new BACE1 inhibitors, as well as thousands of novel alternative drug candidates for eight existing market drugs, including Ceritinib, Ribociclib, Acalabrutinib, Idelalisib, Dabrafenib, Macimorelin, Enzalutamide, and Panobinostat.

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Citations

Oct 21, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Javier VázquezF Javier Luque
Feb 11, 2021·International Journal of Molecular Sciences·Varnavas D MouchlisGeorgia Melagraki
Jun 1, 2021·ACS Omega·Daniel Fernández-LlanezaChristian Tyrchan
Jul 10, 2021·Journal of Chemical Information and Modeling·Biao MaYasushi Okuno
Jul 13, 2021·Journal of Chemical Information and Modeling·Mikołaj SachaStanisław Jastrzębski
Jan 1, 2021·Journal of Chemical Information and Modeling·Kenneth M MerzGuo-Wei Wei
Aug 19, 2021·Journal of Chemical Information and Modeling·Philippe GantzerCarlos Nieto-Draghi
Dec 1, 2020·Journal of Chemical Information and Modeling·Minsup KimArt E Cho
Sep 17, 2021·Journal of Chemical Information and Modeling·Kazuma Kaitoh, Yoshihiro Yamanishi
Sep 30, 2021·Journal of Chemical Information and Modeling·Lizhao HuHongming Chen
Aug 20, 2021·Briefings in Bioinformatics·Fengqing LuXiangxiang Zeng
Nov 10, 2021·The Journal of Physical Chemistry Letters·Kaifu GaoGuo-Wei Wei
Nov 19, 2021·Journal of Chemical Information and Modeling·Sowmya Ramaswamy KrishnanArijit Roy

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