High-power screening (HPS) empowered by DNA-encoded libraries
TLDR
High-power screening (HPS) as discussed by the authors has been proposed for drug discovery in the context of DNA-encoded libraries, which have several orders of magnitude more screening power than HTS.About:
This article is published in Trends in Pharmacological Sciences.The article was published on 2021-11-12 and is currently open access. It has received 24 citations till now. The article focuses on the topics: Druggability & Drug discovery.read more
Citations
More filters
Journal ArticleDOI
Exploration of Ultralarge Compound Collections for Drug Discovery
TL;DR: In this paper , the authors present examples of chemical libraries and spaces and the means used to construct them, and discuss new technologies for searching huge libraries and for searching combinatorially in chemical space.
Journal ArticleDOI
Visible Light-Promoted Divergent Benzoheterocyclization from Aldehydes for DNA-Encoded Chemical Libraries.
TL;DR: A visible light-promoted divergent synthesis of on-DNA benzoheterocycles from aldehydes is presented, demonstrating the feasibility of this approach in DNA-encoded chemical library construction.
Journal ArticleDOI
Photoredox Deaminative Alkylation in DNA-Encoded Library Synthesis.
Yurong Shen,Guanyu Yang,Wei Jan Huang,Alex Shaginian,Qian Lin,Jinqiao Wan,Jin Li,Yun Deng,Guansai Liu +8 more
TL;DR: The deaminative alkylation method is believed to offer a high potential for constructing DNA-encoded libraries, as was demonstrated by the production of a mock library in a 2 × 3 matrix format and confirmation of DNA stability by UPLC-MS and qPCR experiments.
Journal ArticleDOI
Vinyl azide as a synthon for DNA-compatible divergent transformations into N-heterocycles.
TL;DR: A series of DNA-compatible transformations utilizing on-DNA vinyl azide as a synthon to forge divergent N-heterocyclic scaffolds are developed to demonstrate the feasibility of these N- heterocycle syntheses in DNA-encoded chemical library construction.
Journal ArticleDOI
On-DNA Synthesis of Functionalized 4H-Pyran Scaffolds for Focused DNA-Encoded Chemical Libraries.
TL;DR: The functionalized 4H-pyran scaffold is disclosed, combining this scaffold with the merits of scaffold architecture in drug design, and open the door for the construction of DNA-encoded chemical libraries with more consideration for this structural architecture.
References
More filters
Journal ArticleDOI
Design, synthesis and selection of DNA-encoded small-molecule libraries
Matthew A. Clark,Raksha A. Acharya,Christopher C. Arico-Muendel,Svetlana L. Belyanskaya,Dennis Benjamin,Neil R Carlson,Paolo A. Centrella,Cynthia H. Chiu,Steffen Phillip Creaser,John W. Cuozzo,Christopher P. Davie,Yun Ding,G Joseph Franklin,Kurt D Franzen,Malcolm L. Gefter,Steven P Hale,Nils Jakob Vest Hansen,David I. Israel,Jinwei Jiang,Malcolm J. Kavarana,Michael Kelley,Christopher S. Kollmann,Fan Li,Kenneth E Lind,Sibongile Mataruse,Patricia F Medeiros,Jeffrey A. Messer,Paul Myers,Heather O’Keefe,Matthew C Oliff,Cecil E Rise,Alexander L. Satz,Steven R. Skinner,Jennifer L Svendsen,Lujia Tang,Kurt van Vloten,Richard W. Wagner,Gang Yao,Baoguang Zhao,Barry A. Morgan +39 more
TL;DR: An 800-million-member DNA-encoded library in which small molecules are covalently attached to an encoding oligonucleotide is reported, assembled by a combination of chemical and enzymatic synthesis, and interrogated by affinity selection.
Journal ArticleDOI
DNA-Templated Organic Synthesis and Selection of a Library of Macrocycles
TL;DR: This work used multistep DNA-templated organic synthesis to translate libraries of DNA sequences, each containing three “codons,” into libraries of sequence-programmed synthetic small-molecule macrocycles, subjected to in vitro selections for protein affinity.
Journal ArticleDOI
DNA-encoded chemistry: enabling the deeper sampling of chemical space
TL;DR: This Review provides an overview of the development and applications of DNA-encoded chemistry, highlighting the challenges and future directions for the use of this technology.
Journal ArticleDOI
Encoded self-assembling chemical libraries
TL;DR: The use of encoded self-assembling chemical (ESAC) libraries for the facile identification of molecules that bind macromolecular targets was demonstrated by the affinity maturation (>40-fold) of binding molecules to human serum albumin and bovine carbonic anhydrase, leading to binders with dissociation constants in the nanomolar range.
Journal ArticleDOI
DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors.
Philip A. Harris,Bryan W. King,Deepak Bandyopadhyay,Scott B. Berger,Nino Campobasso,Carol A. Capriotti,Julie A. Cox,Lauren Dare,Xiaoyang Dong,Joshua N. Finger,LaShadric C. Grady,Sandra J. Hoffman,Jae U. Jeong,James Kang,Viera Kasparcova,Ami S. Lakdawala,Ruth Lehr,Dean E. McNulty,Rakesh Nagilla,Michael T. Ouellette,Christina S. Pao,Alan R. Rendina,Michelle C. Schaeffer,Jennifer Summerfield,Barbara A. Swift,Rachel D. Totoritis,Paris Ward,Aming Zhang,Daohua Zhang,Robert W. Marquis,John Bertin,Peter J. Gough +31 more
TL;DR: This work elucidate the conformation of RIP1 bound to this benzoxazepinone inhibitor driving its high kinase selectivity and design specific mutations in murine RIP1 to restore potency to levels similar to primate RIP1.