{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Aguilar A"],"funding":["National Cancer Institute","NCI NIH HHS"],"pagination":["19503-19518"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12077404"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(21)"],"pubmed_abstract":["MDM2 has been pursued as an attractive therapeutic target for human cancers. Herein, we describe our discovery of MD-265 as a promising PROTAC MDM2 degrader and extensive <i>in vitro</i> and <i>in vivo</i> evaluations of its therapeutic potential and mechanism of action. MD-265 effectively depleted MDM2 protein in cancer cells at concentrations as low as 1 nM, leading to strong activation of p53 in cancer cells carrying wild-type p53. It selectively inhibited the growth of wild-type p53 leukemia cell lines and showed no activity in mutated p53 lines. MD-265 achieved persistent tumor regression in a leukemia xenograft model without causing any signs of toxicity and dramatically improved survival of mice in a disseminated leukemia model even with a weekly administration. MD-265 displayed an "],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Discovery of MD-265: A Potent MDM2 Degrader That Achieves Complete Tumor Regression and Improves Long-Term Survival of Mice with Leukemia."],"pmcid":["PMC12077404"],"funding_grant_id":["P30 CA046592","P30CA046592","R01CA219345","R01 CA219345"],"pubmed_authors":["Yang J","Li Y","McEachern D","Wang S","Aguilar A","Huang L","Razzouk S"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of MD-265: A Potent MDM2 Degrader That Achieves Complete Tumor Regression and Improves Long-Term Survival of Mice with Leukemia.","description":"MDM2 has been pursued as an attractive therapeutic target for human cancers. Herein, we describe our discovery of MD-265 as a promising PROTAC MDM2 degrader and extensive <i>in vitro</i> and <i>in vivo</i> evaluations of its therapeutic potential and mechanism of action. MD-265 effectively depleted MDM2 protein in cancer cells at concentrations as low as 1 nM, leading to strong activation of p53 in cancer cells carrying wild-type p53. It selectively inhibited the growth of wild-type p53 leukemia cell lines and showed no activity in mutated p53 lines. MD-265 achieved persistent tumor regression in a leukemia xenograft model without causing any signs of toxicity and dramatically improved survival of mice in a disseminated leukemia model even with a weekly administration. MD-265 displayed an ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-05T06:56:11.679Z","creation":"2026-05-13T14:29:20.377Z"},"accession":"S-EPMC12077404","cross_references":{"pubmed":["39480241"],"doi":["10.1021/acs.jmedchem.4c01818"]}}