AF9/ENL-DOT1L PPI-IN-1

AF9/ENL-DOT1L/AF4 PPI-IN-1 is a potent AF9/ENL and histone methyltransferase DOT1L/AF4 protein-protein interactions (PPI) inhibitor. AF9/ENL-DOT1L/AF4 PPI-IN-1 can inhibit the AF9-DOT1L (IC50 = 1.5 μM), AF9-AF4 (IC50 = 1 μM), ENL-AF4 (IC50 = 1.2 μM) interactions. AF9/ENL-DOT1L/AF4 PPI-IN-1 can suppress the expression of Mixed lineage leukemia (MLL) target genes Myc and Meis1 and selectively block the proliferation of MLL-r and several other leukemia cells. AF9/ENL-DOT1L/AF4 PPI-IN-1 exhibits significant antitumor activities in a mouse model of MLL-r leukemia without overt toxicities. AF9/ENL-DOT1L/AF4 PPI-IN-1 can be used for the study of MLL-r leukemia[1].

Product Specifications

UNSPSC

12352005

Target

C-Myc; Epigenetic Reader Domain; Histone Methyltransferase; HOXA

Related Pathways

Apoptosis; Cell Cycle/DNA Damage; Epigenetics

Applications

Cancer-programmed cell death

Field of Research

Cancer

Smiles

FC1=CC=C(OC2=CC=C(NC3=CC=C4N=CC(OCC5CCNCC5)=NC4=C3)C=C2)C=C1.Cl

Molecular Formula

C26H26ClFN4O2

Molecular Weight

480.96

References & Citations

[1]Mishra CB, et al. Synthesis, Structure-Activity Relationships, and Antitumor Activities of Quinoxiline-Containing Inhibitors of the Protein-Protein Interactions between Transcription Coactivator AF9/ENL and DOT1L/AF4. J Med Chem. 2025 Sep 25;68 (18) :19396-19414.