18DS

18DS (also known as CM-625-18DS) is a preclinical-stage, rationally designed chimeric small molecule that acts as a dual inhibitor of class I phosphatidylinositol-3-kinase (PI3K) and bromodomain and extraterminal (BET) proteins. Developed by researchers at Monash University and the Peter MacCallum Cancer Centre, 18DS was synthesized by linking the pharmacophores of the PI3Kα/δ inhibitor ETP-46321 and the BET inhibitor I-BET726. It exhibits high selectivity and nanomolar potency against class I PI3K isoforms (specifically PI3Kα and PI3Kδ) and BET bromodomains (specifically the BD2 domains of BRD2, BRD3, and BRD4). By simultaneously blocking PI3K signaling and displacing BRD4 from chromatin, 18DS synergistically downregulates cMYC transcription and protein stability, overcoming resistance to single-agent therapies. Preclinical studies have demonstrated robust in vitro and in vivo efficacy, including curative responses in mouse models of Eμ-Myc lymphoma, multiple myeloma, and acute myeloid leukemia (AML).

Other names

18D(S)CM-625-18DSCM625-18DSCM 625-18DS