{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:25:33Z","timestamp":1793330733774,"version":"4.5.0"},"reference-count":59,"publisher":"American Society of Hematology","issue":"18","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,29]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Direct targeting of the oncoprotein MYC has not yet been successful. Here we report a novel dual protein degrader, GT19630, which binds directly to MYC and G1 to S phase transition protein 1 (GSPT1). GT19630 disrupts a novel feedforward loop of MYC and GSPT1, in which MYC promotes transcription of GSPT1, and GSPT1 senses the stop codon of MYC to properly terminate its translation. The agent induces an integrated stress response and abrogates oxidative phosphorylation through inhibition of the tricarboxylic acid cycle, resulting in apoptosis. GT19630 has superior activity compared with GSPT1-targeting molecular glues. GT19630 induces profound antiproliferative effects and apoptosis at low nanomolar concentrations in a multitude of leukemia and lymphoma cell lines and primary samples, including those with TP53 mutations. GT19630 is highly active in vivo in models of therapy-resistant hematologic malignancies, including Burkitt lymphoma, acute myeloid leukemia (AML), and multiple myeloma. CD34+ AML blasts overexpress MYC protein compared with normal hematopoietic stem\/progenitor cells (HSPCs), and GT19630 induces greater cytotoxicity in AML cells compared with normal HSPCs. Further, GT19630 restores sensitivity to venetoclax and profoundly prolongs survival in vivo in venetoclax-resistant AML. GT19630 was well tolerated in humanized Crbn mice. In conclusion, our data support the development of the MYC\/GSPT1 degrader GT19630 as a therapeutic strategy for MYC-driven hematologic malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025030170","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:24:07Z","timestamp":1786987447000},"page":"2278-2293","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":2,"title":["A dual MYC and GSPT1 protein degrader for MYC-driven hematologic malignancies"],"prefix":"10.1182","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5827-7406","authenticated-orcid":false,"given":"Yuki","family":"Nishida","sequence":"first","affiliation":[{"name":"1Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, 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