Evidence map›Paper›PMID 37582753›Full record

ArticleNature communications2023

Diversity-oriented synthesis encoded by deoxyoligonucleotides.

Liam Hudson, Jeremy W Mason, Matthias V Westphal, Matthieu J R Richter, Jonathan R Thielman, Bruce K Hua, Christopher J Gerry, Guoqin Xia, Heather L Osswald, John M Knapp and 24 more

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
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  7. Article
  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors.

Liam HudsonChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0009-0000-8844-0059
Jeremy W MasonChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.
Matthias V WestphalChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-0693-0789
Matthieu J R RichterChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.
Jonathan R ThielmanChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-8677-5071
Bruce K HuaChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-7330-2312
Christopher J GerryChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-7602-0492
Guoqin XiaDepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0001-7666-9550
Heather L OsswaldDepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
John M KnappChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.
Zher Yin TanChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.
Praveen KokkondaChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.
Ben I C TrescoChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.
Shuang LiuChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-3287-2404
Andrew G ReidenbachChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.
Katherine S LimChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-0391-6877
Jennifer PoirierNovartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.
John CapeceNovartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Simone BonazziNovartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Christian M GampeNovartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Nichola J SmithNovartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-3799-0074
James E BradnerNovartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-2718-4415
Connor W ColeyChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-8271-8723
Paul A ClemonsChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-1800-5112
Bruno MelilloDepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0002-9708-5287
C Suk-Yee HonChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.
Johannes OttlNovartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, CH-4002, Basel, Switzerland.
Christoph E DumelinNovartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, CH-4002, Basel, Switzerland.
Jonas V SchaeferNovartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, CH-4002, Basel, Switzerland.ORCID http://orcid.org/0000-0002-8332-4371
Ann Marie E FaustNovartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-7468-5984
Frédéric BerstNovartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, CH-4002, Basel, Switzerland.
Stuart L SchreiberChemical Biology and Therapeutics Science Program, Broad Institute, 415 Main Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-1922-7558
Frédéric J ZécriNovartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA. frederic.zecri@novartis.com.ORCID http://orcid.org/0000-0002-2469-8875
Karin BrinerNovartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.

Funding

Targeting vulnerabilities of therapy-resistant cancer cell states with small moleculesU01CA217848 · NCI · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2017 to 2021
$5.8M
Studies of Materials with Physiological PropertiesR35GM127045 · NIGMS · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2018 to 2022
$3.2M
Translating novel cancer targets and mechanisms from the CTD^2 Network using molecular gluesU01CA272612 · NCI · BROAD INSTITUTE, INC. · PI CLEMONS, PAUL ANDREW, SCHREIBER, STUART L · 2022 to 2023
$1.9M
NCI NIH HHS U01 CA217848NCI NIH HHS U01 CA272612NIGMS NIH HHS R35 GM127045
6 · The paper itself

Abstract

Diversity-oriented synthesis (DOS) is a powerful strategy to prepare molecules with underrepresented features in commercial screening collections, resulting in the elucidation of novel biological mechanisms. In parallel to the development of DOS, DNA-encoded libraries (DELs) have emerged as an effective, efficient screening strategy to identify protein binders. Despite recent advancements in this field, most DEL syntheses are limited by the presence of sensitive DNA-based constructs. Here, we describe the design, synthesis, and validation experiments performed for a 3.7 million-member DEL, generated using diverse skeleton architectures with varying exit vectors and derived from DOS, to achieve structural diversity beyond what is possible by varying appendages alone. We also show screening results for three diverse protein targets. We will make this DEL available to the academic scientific community to increase access to novel structural features and accelerate early-phase drug discovery.

Indexed as

Drug DiscoverySmall Molecule LibrariesDNAGene LibraryDNASmall Molecule Libraries

Identifiers

PMID37582753
PMCPMC10427684

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.