Exploration of Ultralarge Compound Collections for Drug Discovery

被引：87

作者：

Warr, Wendy A. ^{[4
]}

Nicklaus, Marc C. ^{[1
]}

Nicolaou, Christos A. ^{[2
]}

Rarey, Matthias ^{[3
]}

机构：

[1] NCI Frederick, NCI, NIH, CADD Grp, Frederick, MD 21702 USA

[2] Eli Lilly & Co, Lilly Res Labs, Discovery Chem, Indianapolis, IN 46285 USA

[3] Univ Hamburg, ZBH Ctr Bioinformat, D-20146 Hamburg, Germany

[4] Wendy Warr & Associates, Holmes Chapel CW4 7HZ, Cheshire, England

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2022年 / 62卷 / 09期

关键词：

review; ultralarge libraries; chemical space; drug design; structure search; navigating chemical space; DNA-encoded libraries; de novo drug design; fragment-based drug design; generative models; autonomous laboratory; DE-NOVO DESIGN; CHEMICAL UNIVERSE; VIRTUAL EXPLORATION; SCAFFOLD TOPOLOGIES; SMALL MOLECULES; RING-SYSTEMS; DATABASE; CHEMISTRY; VISUALIZATION; DIGITIZATION;

D O I：

10.1021/acs.jcim.2c00224

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Designing new medicines more cheaply and quicklyis tightly linked to the quest of exploring chemical space morewidely and efficiently. Chemical space is monumentally large, butrecent advances in computer software and hardware have enabledresearchers to navigate virtual chemical spaces containing billionsof chemical structures. This review specifically concerns collectionsof many millions or even billions of enumerated chemicalstructures as well as even larger chemical spaces that are notfully enumerated. We present examples of chemical libraries andspaces and the means used to construct them, and we discuss newtechnologies for searching huge libraries and for searchingcombinatorially in chemical space. We also cover space navigationtechniques and consider new approaches tode novodrug designand the impact of the"autonomous laboratory"on synthesis of designed compounds. Finally, we summarize some other challengesand opportunities for the future.

引用

页码：2021 / 2034

页数：14

共 156 条

[51] Combining Cloud-Based Free-Energy Calculations, Synthetically Aware Enumerations, and Goal-Directed Generative Machine Learning for Rapid Large-Scale Chemical Exploration and Optimization [J].

Ghanakota, Phani ;

Bos, Pieter H. ;

Konze, Kyle D. ;

Staker, Joshua ;

Marques, Gabriel ;

Marshall, Kyle ;

Leswing, Karl ;

Abel, Robert ;

Bhat, Sathesh .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2020, 60 (09) :4311-4325

[52] DNA-Encoded Chemical Libraries: A Comprehensive Review with Succesful Stories and Future Challenges [J].

Gironda-Martinez, Adrian ;

Donckele, Etienne J. ;

Samain, Florent ;

Neri, Dario .

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, 2021, 4 (04) :1265-1279

[53] Pharmacophore Model for SARS-CoV-2 3CLpro Small-Molecule Inhibitors and in Vitro Experimental Validation of Computationally Screened Inhibitors [J].

Glaab, Enrico ;

Manoharan, Ganesh Babu ;

Abankwa, Daniel .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2021, 61 (08) :4082-4096

[54] A remote-controlled adaptive medchem lab: an innovative approach to enable drug discovery in the 21st Century [J].

Godfrey, Alexander G. ;

Masquelin, Thierry ;

Hemmerle, Horst .

DRUG DISCOVERY TODAY, 2013, 18 (17-18) :795-802

[55] InChI version 1.06: now more than 99.99% reliable [J].

Goodman, Jonathan M. ;

Pletnev, Igor ;

Thiessen, Paul ;

Bolton, Evan ;

Heller, Stephen R. .

JOURNAL OF CHEMINFORMATICS, 2021, 13 (01)

[56]

Goodman JM, 2018, APPLIED CHEMOINFORMATICS: ACHIEVEMENTS AND FUTURE OPPORTUNITIES, P86

[57] An open-source drug discovery platform enables ultra-large virtual screens [J].

Gorgulla, Christoph ;

Boeszoermenyi, Andras ;

Wang, Zi-Fu ;

Fischer, Patrick D. ;

Coote, Paul W. ;

Padmanabha Das, Krishna M. ;

Malets, Yehor S. ;

Radchenko, Dmytro S. ;

Moroz, Yurii S. ;

Scott, David A. ;

Fackeldey, Konstantin ;

Hoffmann, Moritz ;

Iavniuk, Iryna ;

Wagner, Gerhard ;

Arthanari, Haribabu .

NATURE, 2020, 580 (7805) :663-+

[58] Virtual Screening in the Cloud: How Big Is Big Enough? [J].

Grebner, Christoph ;

Malmerberg, Erik ;

Shewmaker, Andrew ;

Batista, Jose ;

Nicholls, Anthony ;

Sadowski, Jens .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2020, 60 (09) :4274-4282

[59]

Green DVS, 2020, J COMPUT AID MOL DES, V34, P747, DOI 10.1007/s10822-019-00234-8

[60] Generative Recurrent Networks for De Novo Drug Design [J].

Gupta, Anvita ;

Mueller, Alex T. ;

Huisman, Berend J. H. ;

Fuchs, Jens A. ;

Schneider, Petra ;

Schneider, Gisbert .

MOLECULAR INFORMATICS, 2018, 37 (1-2)

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