Evidence map›Paper›PMID 42020383›Full record

ArticleNature communications2026

Discovery of molecular glues that bind FKBP12 and structurally distinct targets using DNA-encoded libraries.

Trevor A Zandi, Michael J Romanowski, Jessica S Viscomi, Karl Gunderson, Zher Yin Tan, Bingqi Tong, Simone Bonazzi, Frédéric J Zécri, Stuart L Schreiber, Gregory A Michaud

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Trevor A ZandiGlobal Discovery Chemistry, Novartis Biomedical Research, Cambridge, MA, USA.
Michael J RomanowskiDiscovery Sciences, Novartis Biomedical Research, Cambridge, MA, USA.
Jessica S ViscomiDiscovery Sciences, Novartis Biomedical Research, Cambridge, MA, USA.
Karl GundersonGlobal Discovery Chemistry, Novartis Biomedical Research, Cambridge, MA, USA.
Zher Yin TanBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2498-043X
Bingqi TongGlobal Discovery Chemistry, Novartis Biomedical Research, Cambridge, MA, USA.
Simone BonazziGlobal Discovery Chemistry, Novartis Biomedical Research, Basel, Switzerland.
Frédéric J ZécriGlobal Discovery Chemistry, Novartis Biomedical Research, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2469-8875
Stuart L SchreiberBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1922-7558
Gregory A MichaudDiscovery Sciences, Novartis Biomedical Research, Cambridge, MA, USA. gregory.michaud@novartis.com.ORCID http://orcid.org/0000-0003-3954-4921

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Molecular glues are small molecules that engage their target and presenter proteins cooperatively. FKBP12 molecular glues (FK506 and rapamycin) were discovered several decades ago and have been used clinically, but our understanding of the breadth of FKBP12 molecular glues and targets has yet to be fully revealed. To expand the target classes of FKBP12 molecular glues, we construct and screen a multi-million-member non-macrocyclic FKBP12-ligand DNA-encoded library using 25 structurally distinct proteins. Synthesis and validation of select hits in biophysical and cell-based assays confirm FKBP12-dependent molecular-glue recruitment to bromodomain-containing protein 9 (BRD9) and quinoid dihydropteridine reductase (QDPR). One glue shows no measurable binding to QDPR alone but has appreciable binding in the presence of FKBP12 using either purified proteins or intact cells. The sites of recruitment are characterized with mutational analysis, competition-based methods and X-ray crystallography. The results of this study confirm that FKBP12-binding DELs can yield molecular glues generating highly selective FKBP12-target protein interactions.

Indexed as

DNATacrolimus Binding Protein 1ACrystallography, X-RayGene LibraryHumansLigandsModels, MolecularProtein BindingSirolimusDNALigandsSirolimusTacrolimus Binding Protein 1A

Identifiers

PMID42020383
PMCPMC13287777

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.