{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301413/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301413"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of a paralog-selective p300 protein degrader with potent anti-cancer activity in hematological malignancies","description":"The E1A-associated protein p300 (EP300) is a key regulator of oncogenic transcription factors, making it a promising target for cancer therapy. However, high sequence similarity to its paralog, CREB-binding protein (CBP), has hindered the development of selective inhibitors, leading to toxic side effects. Here, we describe a highly potent and selective p300 degrader. Unlike dual p300/CBP degraders, this compound forms a stronger, more stable ternary complex with p300, induces higher level of p300 ubiquitination and recruitment to the proteosome, and ubiquitinates a unique lysine site on p300. Hematological cancers, including multiple myeloma, non-Hodgkin’s lymphoma and acute myeloid leukemia, showed the greatest sensitivity to the p300-selective degrader, which induced a lethal phenotype in cells and demonstrated antitumor efficacy in xenograft models. These findings highlight the therapeutic potential of selective p300 degradation as a novel strategy for the treatment of hematological malignancies and the inhibition of cancer progression.","dates":{"publication":"2026/02/26"},"accession":"GSE301413","cross_references":{"GSM":["GSM9082751","GSM9082750","GSM9082753","GSM9082752","GSM9082755","GSM9082754","GSM9082748","GSM9082749","GSM9396779","GSM9396786","GSM9396785","GSM9396784","GSM9396783","GSM9396782","GSM9396781","GSM9396780"],"GPL":["20301"],"GSE":["301413"],"taxon":["Homo sapiens"]}}