{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wu F"],"funding":["Breast Cancer Research Foundation","U.S. Department of Defense","Susan G. Komen for the Cure","National Cancer Institute","NCI NIH HHS","Cancer Prevention and Research Institute of Texas"],"pagination":["4716-4731"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7340344"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["63(9)"],"pubmed_abstract":["Histone acetyltransferase (HAT) p300 and its paralog CBP acetylate histone lysine side chains and play critical roles in regulating gene transcription. The HAT domain of p300/CBP is a potential drug target for cancer. Through compound screening and medicinal chemistry, novel inhibitors of p300/CBP HAT with their IC<sub>50</sub> values as low as 620 nM were discovered. The most potent inhibitor is competitive against histone substrates and exhibits a high selectivity for p300/CBP. It inhibited cellular acetylation and had strong activity with EC<sub>50</sub> of 1-3 μM against proliferation of several tumor cell lines. Gene expression profiling in estrogen receptor (ER)-positive breast cancer MCF-7 cells showed that inhibitor treatment recapitulated siRNA-mediated p300 knockdown, inhibited ER-mediated gene transcription, and suppressed expression of numerous cancer-related gene signatures. These results demonstrate that the inhibitor is not only a useful probe for biological studies of p300/CBP HAT but also a pharmacological lead for further drug development targeting cancer."],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Discovery, Structure-Activity Relationship, and Biological Activity of Histone-Competitive Inhibitors of Histone Acetyltransferases P300/CBP."],"pmcid":["PMC7340344"],"funding_grant_id":["17-143","U54 CA233223","PG12221410","P50 CA186784","P50CA58183","RP180177","RP150129","18-145","16-142","P50 CA058183","P30 CA125123","W81XWH-14-1-0326"],"pubmed_authors":["Hua Y","Nie S","Wu J","Davis CM","Coarfa C","Fu X","Lin YL","Kaochar S","Wu F","Yao Y","Ehli EA","Schiff R","Mitsiades N","Robertson M","Wu X","Song Y"],"additional_accession":[]},"is_claimable":false,"name":"Discovery, Structure-Activity Relationship, and Biological Activity of Histone-Competitive Inhibitors of Histone Acetyltransferases P300/CBP.","description":"Histone acetyltransferase (HAT) p300 and its paralog CBP acetylate histone lysine side chains and play critical roles in regulating gene transcription. The HAT domain of p300/CBP is a potential drug target for cancer. Through compound screening and medicinal chemistry, novel inhibitors of p300/CBP HAT with their IC<sub>50</sub> values as low as 620 nM were discovered. The most potent inhibitor is competitive against histone substrates and exhibits a high selectivity for p300/CBP. It inhibited cellular acetylation and had strong activity with EC<sub>50</sub> of 1-3 μM against proliferation of several tumor cell lines. Gene expression profiling in estrogen receptor (ER)-positive breast cancer MCF-7 cells showed that inhibitor treatment recapitulated siRNA-mediated p300 knockdown, inhibited ER-mediated gene transcription, and suppressed expression of numerous cancer-related gene signatures. These results demonstrate that the inhibitor is not only a useful probe for biological studies of p300/CBP HAT but also a pharmacological lead for further drug development targeting cancer.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 May","modification":"2026-05-02T14:39:07.649Z","creation":"2026-04-07T18:07:17.427Z"},"accession":"S-EPMC7340344","cross_references":{"pubmed":["32314924"],"doi":["10.1021/acs.jmedchem.9b02164"]}}