NICE-01

NICE-01 (AP1867-PEG2-JQ1) is a bifunctional small molecule designed as a chemical inducer of proximity (CIP) to rewire the transcriptional activity of the MECOM (MDS1 and EVI1 complex locus) protein. It consists of an AP1867 moiety, which selectively binds to the FKBP12F36V mutant tag, and a JQ1 moiety, which binds to the bromodomain-containing protein 4 (BRD4). In experimental models of high-risk acute myeloid leukemia (AML) where MECOM is endogenously tagged with FKBP12F36V, NICE-01 recruits the epigenetic activator BRD4 to MECOM-bound genomic sites. This recruitment converts MECOM from a transcriptional repressor into an activator, triggering a pro-differentiation gene program and inducing leukemia cell death. Developed by researchers at Harvard Medical School and the Broad Institute, NICE-01 serves as a proof-of-concept for the therapeutic rewiring of stem cell gene regulatory networks in cancers driven by transcription factor dysregulation.