TRAP-1

TRAP-1 (XJZ-06-462) is a transcriptional activator of p53 (TRAP) with JQ-1 carboxylic acid as its target protein ligand. TRAP-1 forms a ternary complex with p53 Y220C and BRD4, potently activates p53 transcription, and inhibits the growth and proliferation of tumor cells. TRAP-1 upregulates p21 and other p53 target genes in pancreatic cell lines carrying p53 Y220C, and induces cellular senescence and apoptosis. TRAP-1 can be used in cancer research involving p53 Y220C -carrying tumors ^[1]. (Pink: BRD4 ligand; Blue: E3 ligase ligand; Black: linker).

In Vitro, TRAP-1 (0.1 nM-10 μM; 15 min) potently and specifically induces proximity between purified p53Y220C DNA binding domain and BRD4BD1, with no activity toward wild-type p53^[1]. TRAP-1 (0.1-10 μM; 24 h) induces potent, dose-dependent p53-mediated transcriptional activation in p53Y220C-expressing BxPC-3 cells^[1]. TRAP-1 (1-10 μM; 4 h) induces a stable interaction between BRD4 and p53Y220C in transfected HEK293T cells^[1]. TRAP-1 (1, 3 μM; 2-24 h) induces robust, time-dependent upregulation of p53 target genes (MDM2, CDKN1A, BBC3) in p53Y220C-expressing BxPC-3 cells; induces rapid and robust upregulation of p21 and MDM2 protein levels in p53Y220C-expressing BxPC-3 cells^[1]. TRAP-1 (2 μM; 2 h pulse, 72 h compound-free) is sufficient to induce persistent inhibition of cell proliferation in p53Y220C-expressing BxPC-3 cells^[1]. TRAP-1 (0.001-10 μM; 72, 120 h) exhibits potent, mutant-selective antiproliferative activity against p53Y220C-expressing cells^[1].

References:
[1]. Zhu X, et al. Activating p53Y220C with a mutant-specific small molecule. Nat Commun. 2026.