{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["39(9)"],"submitter":["Vick EJ"],"pubmed_abstract":["IRAK4 is a therapeutic target in myeloid malignancies, but current IRAK4 inhibitors show only modest clinical efficacy in acute myeloid leukemia, highlighting the need for combination strategies. To identify drugs with synergistic potential alongside IRAK4 inhibitors, we conducted a high-throughput screen of 2803 investigational and approved drugs in isogenic IRAK4-deficient and wild-type human AML cells. The top hit from this screen was the Cereblon E3 ligase modulator (CELMoD) CC-885. Validation in vitro and in vivo confirmed that CC-885 and related CELMoDs synergize with IRAK4 inhibitors to suppress leukemic cells. Among CC-885 substrates, GSPT1 loss showed the most pronounced effects in IRAK4-inhibited leukemic cells. Transcriptional and proteomic analyses revealed that CC-885 treatmen"],"journal":["Leukemia"],"pagination":["2163-2173"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12380595"],"repository":["biostudies-literature"],"pubmed_title":["Targeting of IRAK4 and GSPT1 enhances therapeutic efficacy in AML via c-Myc destabilization."],"pmcid":["PMC12380595"],"pubmed_authors":["Vick EJ","Klumpp-Thomas C","Culver-Cochran AE","Starczynowski DT","Choi K","Holland D","Thomas CJ","Bennett J","Hueneman K","Clough CA","Ceribelli M","Hassan A","Zhang X","McKnight C","Greis KD","Muto T","Bolanos LC","Wunderlich M"],"additional_accession":[]},"is_claimable":false,"name":"Targeting of IRAK4 and GSPT1 enhances therapeutic efficacy in AML via c-Myc destabilization.","description":"IRAK4 is a therapeutic target in myeloid malignancies, but current IRAK4 inhibitors show only modest clinical efficacy in acute myeloid leukemia, highlighting the need for combination strategies. To identify drugs with synergistic potential alongside IRAK4 inhibitors, we conducted a high-throughput screen of 2803 investigational and approved drugs in isogenic IRAK4-deficient and wild-type human AML cells. The top hit from this screen was the Cereblon E3 ligase modulator (CELMoD) CC-885. Validation in vitro and in vivo confirmed that CC-885 and related CELMoDs synergize with IRAK4 inhibitors to suppress leukemic cells. Among CC-885 substrates, GSPT1 loss showed the most pronounced effects in IRAK4-inhibited leukemic cells. Transcriptional and proteomic analyses revealed that CC-885 treatmen","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-05-10T04:36:14.865Z","creation":"2026-04-08T01:30:18.811Z"},"accession":"S-EPMC12380595","cross_references":{"pubmed":["40670672"],"doi":["10.1038/s41375-025-02695-3"]}}