ArticleJournal of the American Chemical Society2021
A Dual-Site Inhibitor of CBP/p300 KIX is a Selective and Effective Modulator of Myb.
Article in Journal of the American Chemical Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting a Leukemia-Relevant Protein-Protein Interface: N-Aryl Anthranilic Acids as Disruptors of the c-Myb-CBP/p300 KIX Interaction.Chemical biology & drug design · 2026Article
- De Novo Design of Multivalent α/β-Peptides Mimicking Transcription Factors Targeting the CBP KIX Domain.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Dual PROTACs Versus Dual Inhibitors in Oncology: A Medicinal Chemistry and Linker Design Perspective.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Discovery of peptidomimetic inhibitors of CREB/CBP by targeting hydrophobic grooves on the surface of the CBP KIX domain.Acta pharmaceutica Sinica. B · 2025Article
- Targeting histone H2B acetylated enhanceosomes via p300/CBP degradation in prostate cancer.Nature genetics · 2025Article
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- Selective CBP/EP300 Bromodomain Inhibitors: Novel Epigenetic Tools to Counter TNF-α-Driven Inflammation.JACS Au · 2025Article
- Recognition of the CREB-Binding Protein/Mixed Lineage Leukemia Interface by Sulfonyl-γ-AApeptides: Beyond Mimicry of Mixed Lineage Leukemia.Journal of medicinal chemistry · 2025Article
- Review
- High-throughput affinity measurements of direct interactions between activation domains and co-activators.bioRxiv : the preprint server for biology · 2024Article
- A Lipopeptidomimetic of Transcriptional Activation Domains Selectively Disrupts the Coactivator Med25 Protein-Protein Interactions.Angewandte Chemie (International ed. in English) · 2024Article
- Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition.Nature communications · 2024Article
- Transcription Factor MYB as Therapeutic Target: Current Developments.International journal of molecular sciences · 2024Review
- Inhibition of CREB Binding and Function with a Dual-Targeting Ligand.Biochemistry · 2024Article
- Emerging role of MYB transcription factors in cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- MYB as a Critical Transcription Factor and Potential Therapeutic Target in AML.Advances in experimental medicine and biology · 2024Review
- Garcinolic Acid Distinguishes Between GACKIX Domains and Modulates Interaction Networks.Chembiochem : a European journal of chemical biology · 2023Article
- Rational peptide design for inhibition of the KIX-MLL interaction.Scientific reports · 2023Article
- Effects of the Acetyltransferase p300 on Tumour Regulation from the Novel Perspective of Posttranslational Protein Modification.Biomolecules · 2023Review
- Synthetic oleanane triterpenoids suppressFrontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The protein-protein interaction between the KIX motif of the transcriptional coactivator CBP/p300 and the transcriptional activator Myb is a high-value target due to its established role in certain acute myeloid leukemias (AML) and potential contributions to other cancers. However, the CBP/p300 KIX domain has multiple binding sites, several structural homologues, many binding partners, and substantial conformational plasticity, making it challenging to specifically target using small-molecule inhibitors. Here, we report a picomolar dual-site inhibitor (MybLL-tide) of the Myb-CBP/p300 KIX interaction. MybLL-tide has higher affinity for CBP/p300 KIX than any previously reported compounds while also possessing 5600-fold selectivity for the CBP/p300 KIX domain over other coactivator domains. MybLL-tide blocks the association of CBP and p300 with Myb in the context of the proteome, leading to inhibition of key Myb·KIX-dependent genes in AML cells. These results show that MybLL-tide is an effective, modifiable tool to selectively target the KIX domain and assess transcriptional effects in AML cells and potentially other cancers featuring aberrant Myb behavior. Additionally, the dual-site design has applicability to the other challenging coactivators that bear multiple binding surfaces.
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Registered trials
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.