ArticleMolecular cancer therapeutics2013
Small-molecule inhibitors of acetyltransferase p300 identified by high-throughput screening are potent anticancer agents.
Article in Molecular cancer therapeutics, 2013. 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 51 papers.
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Who cites it
51 citing papers in PubMed, 101 citations in OpenAlex.
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- Emerging Approaches in Breast Cancer: From Molecular Mechanisms to Diagnosis and Therapeutic Strategies.Oncology research · 2026Review
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- The role of lactylation in breast cancer development: mechanisms, clinical translation and new strategies for treatment.Frontiers in oncology · 2025Review
- Potential role of lactylation in intrinsic immune pathways in lung cancer.Frontiers in pharmacology · 2025Review
- Genetic dysregulation of EP300 in cancers in light of cancer epigenome control - targeting of p300-proficient and -deficient cancers.Molecular therapy. Oncology · 2024Review
- Bromodomain proteins as potential therapeutic targets for B-cell non-Hodgkin lymphoma.Cell & bioscience · 2024Review
- Roles of posttranslational modifications in lipid metabolism and cancer progression.Biomarker research · 2024Review
- Identification of small molecules that are synthetically lethal upon knockout of the RNA ligase Rlig1 in human cells.RSC chemical biology · 2024Article
- Acetyltransferase P300 Regulates Glucose Metabolic Reprogramming through Catalyzing Succinylation in Lung Cancer.International journal of molecular sciences · 2024Article
- Integrating text mining with network models for successful target identification:Frontiers in pharmacology · 2024Article
- EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.International journal of molecular sciences · 2023Review
- KAT7 promotes radioresistance through upregulating PI3K/AKT signaling in breast cancer.Journal of radiation research · 2023Article
- Effects of the Acetyltransferase p300 on Tumour Regulation from the Novel Perspective of Posttranslational Protein Modification.Biomolecules · 2023Review
- Intersection of immune and oncometabolic pathways drives cancer hyperprogression during immunotherapy.Cancer cell · 2023Article
- Post-Translational Modifications by Lipid Metabolites during the DNA Damage Response and Their Role in Cancer.Biomolecules · 2022Review
- Modulating Microbiota as a New Strategy for Breast Cancer Prevention and Treatment.Microorganisms · 2022Review
- Article
- Structure-activity relationship and antitumor activity of 1,4-pyrazine-containing inhibitors of histone acetyltransferases P300/CBP.European journal of medicinal chemistry · 2022Article
- The role of protein acetylation in carcinogenesis and targeted drug discovery.Frontiers in endocrinology · 2022Review
Corrections and comments
- Erratum issuedChase, Peter [added]
Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
Acetyltransferase p300 (KAT3B) plays key roles in signaling cascades that support cancer cell survival and sustained proliferation. Thus, p300 represents a potential anticancer therapeutic target. To discover novel anticancer agents that target p300, we conducted a high-throughput screening campaign. A library of 622,079 compounds was assayed for cytotoxicity to the triple-negative breast cancer (TNBC) cell line MDA-MB-231 but not to the human mammary epithelial cells. The resulting compounds were tested in a biochemical assay for inhibiting the enzymatic activity of p300. One compound (L002, NSC764414) displayed an IC50 of 1.98 μmol/L against p300 in vitro, inhibited acetylation of histones and p53, and suppressed STAT3 activation in cell-based assays. L002 could be docked to the active site of the p300 catalytic domain. Biochemical tests of a series of related compounds revealed functional groups that may impact inhibitory potency of L002 against p300. Interestingly, these analogs showed inhibitory activities against the cellular paralog of p300 (CBP), p300/CBP-associated factor, and GCN5, but not to other acetyltransferases (KAT5, KAT6B, and KAT7), histone deacetylases, and histone methyltransferases. Among the NCI-60 panel of cancer cell lines, leukemia and lymphoma cell lines were extremely sensitive to L002, whereas it is toxic to only a limited number of cell lines derived from solid tumors. Notably, breast cancer cell lines, especially those derived from TNBC, were highly susceptible to L002. In vivo, it potently suppressed tumor growth and histone acetylation of MDA-MB-468 xenografts. Thus, these new acetyltransferase inhibitors are potential anticancer therapeutics.
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