Evidence map›Paper›PMID 40165709›Full record

ArticleChemMedChem2025

Development of C646-Based Proteolysis Targeting Chimeras Degraders of the Lysine Acetyltransferases CBP and p300.

Francesco Fiorentino, Filippo Spriano, Daniela Tomaselli, Giorgia Risi, Emanuele Fabbrizi, Valeria Pecci, Simona Nanni, Francesco Bertoni, Dante Rotili, Antonello Mai

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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.

Francesco FiorentinoDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy.ORCID https://orcid.org/0000-0003-3550-1860
Filippo SprianoFaculty of Biomedical Sciences, Institute of Oncology Research, USI Bellinzona, 6500, Bellinzona, Switzerland.ORCID https://orcid.org/0000-0002-8615-1568
Daniela TomaselliDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy.ORCID https://orcid.org/0000-0002-3866-8386
Giorgia RisiFaculty of Biomedical Sciences, Institute of Oncology Research, USI Bellinzona, 6500, Bellinzona, Switzerland.
Emanuele FabbriziDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy.ORCID https://orcid.org/0000-0002-3850-7750
Valeria PecciDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168, Rome, Italy.ORCID https://orcid.org/0000-0001-9170-3593
Simona NanniDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168, Rome, Italy.ORCID https://orcid.org/0000-0002-3320-1584
Francesco BertoniFaculty of Biomedical Sciences, Institute of Oncology Research, USI Bellinzona, 6500, Bellinzona, Switzerland.ORCID https://orcid.org/0000-0001-5637-8983
Dante RotiliDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy.ORCID https://orcid.org/0000-0002-8428-8763
Antonello MaiDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy.ORCID https://orcid.org/0000-0001-9176-2382

Funding

AIRC IG 2019-ID 22858Italian Ministry of University FISR2019_00374 MeDyCaRegione Lazio 2020 - A0375-2020-36597Sapienza University of Rome RM12117A61C811CESapienza University of Rome TACKLE
6 · The paper itself

Abstract

The alteration of the lysine acetyltransferase activity and protein-protein interactions of the transcriptional co-activators CREB-binding protein (CBP) and p300 is linked to the development of both solid and hematological cancers. To target both functions of CBP/p300, two PROTAC-based chemical degraders are developed by linking the CBP/p300 catalytic inhibitor C646 and the Cereblon (CRBN) ligand thalidomide via polyethylene glycol-based linkers. Both compounds exhibit submicromolar inhibition of CBP/p300 and decrease their levels in the SU-DHL-10 lymphoma cell line at low-micromolar concentrations. Moreover, it is demonstrated that compound 1 recruits CBP/p300 and CRBN in cells and acts as a bona fide PROTAC degrader of CBP/p300 via the ubiquitin-proteasome pathway. Finally, both compounds exhibit low-micromolar antiproliferative activity in different lymphoma cell lines and are more potent than C646. Overall, it is demonstrated that the PROTAC strategy is a viable option for targeting CBP/p300 in lymphoma and identifies compound 1 as a promising chemical tool and lead compound for further studies.

Indexed as

Antineoplastic AgentsCREB-Binding ProteinDrug DevelopmentE1A-Associated p300 ProteinEnzyme Inhibitorsp300-CBP Transcription FactorsThalidomideAdaptor Proteins, Signal TransducingBenzoatesCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansMolecular StructureNitrobenzenes4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidAdaptor Proteins, Signal TransducingAntineoplastic AgentsBenzoatesCRBN protein, humanCREB-Binding ProteinCREBBP protein, humanE1A-Associated p300 ProteinEnzyme InhibitorsEP300 protein, humanNitrobenzenesp300-CBP Transcription FactorsProteolysis Targeting ChimeraPyrazolonesThalidomideUbiquitin-Protein Ligasesacetylationepigeneticslymphomaproteolysis targeting chimerastargeted degradation

Identifiers

PMID40165709
PMCPMC12174726

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.