title: Chemical Space Mimicry for Drug Discovery.
abstract: We describe a new library generation method, Machine-based Identification of Molecules Inside Characterized Space (MIMICS), that generates sets of molecules inspired by a text-based input. MIMICS-generated libraries were found to preserve distributions of properties while simultaneously increasing structural diversity. Newly identified MIMICS-generated compounds were found to be bioactive as inhibitors of specific components of the unfolded protein response (UPR) and the VEGFR2 pathway in cell-based assays, thus confirming the applicability of this methodology toward drug design applications. Wider application of MIMICS could facilitate the efficient utilization of chemical space.
authors.affiliation: Trinity College, University of Oxford , Oxford OX1 3BH, United Kingdom.|Department of Radiation Oncology, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: William
authors.identifier: 0000-0002-2682-0416
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Dadi
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Dhanya K
authors.initials: DK
authors.lastname: Nambiar
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New Zealand.
authors.forename: Lydia P
authors.initials: LP
authors.lastname: Liew
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland , Auckland, New Zealand.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hay
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Joshua
authors.initials: J
authors.lastname: Bloomstein
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Brandon
authors.initials: B
authors.lastname: Turner
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Quynh-Thu
authors.initials: QT
authors.lastname: Le
authors.affiliation: Department of Statistics, Stanford University , Stanford, California 94305, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Tibshirani
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine , Stanford, California 94305, United States.|Institute for Immunity, Transplantation, and Infection & Division of Biomedical Informatics Research, Department of Medicine, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Purvesh
authors.initials: P
authors.lastname: Khatri
authors.affiliation: Chemistry Research Laboratory, University of Oxford , Oxford OX1 3TA, United Kingdom.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Moloney
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Koong
mesh_terms: D055808:Drug Discovery / Q000379:methods*; D016571:Neural Networks, Computer; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2