Poster #067, Charles R. Drew University of Medicine and Science
Novel Small-Molecule Compound CPD-191 Selectively Targets Acute Myeloid Leukemia Cells
Mentor: Ke Wu, MD, PhD
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that continues to require more effective and selective therapeutic strategies. CPD-191 is a novel small-molecule compound with potential anti-leukemic activity. To evaluate the potency, selectivity, apoptosis-inducing effects, and early impact on MCL-1 protein signaling of CPD-191 in AML cell models. MV4-11 and MOLM-13 AML cells were treated with increasing concentrations of CPD-191 for 72 hours. Cell viability was measured using CellTiter-Glo, and IC50 values were calculated from dose-response curves. Selectivity was assessed in peripheral blood mononuclear cells (PBMCs) and BJ fibroblasts. Apoptosis was measured in MV4-11 cells after treatment with 10 or 20 nM CPD-191 using Annexin V/PI flow cytometry. MCL-1 protein signal was evaluated by flow cytometry. CPD-191 potently inhibited AML cell viability, with IC50 values of 3.7 nM in MV4-11 cells and 9.8-10.3 nM in MOLM-13 cells. Cytotoxicity was substantially lower in non-leukemic cells, with IC50 values of approximately 3.0-3.3 micromolar in PBMCs and 6.2 micromolar in BJ fibroblasts. CPD-191 induced dose- and time-dependent apoptosis in MV4-11 cells. At 20 nM, total apoptosis increased from 15.7% at 6 hours to 40.2% at 24 hours, 92.2% at 48 hours, and 97.1% at 72 hours. MCL-1 protein signal decreased by
approximately 15-25% within 2-6 hours. CPD-191 demonstrates potent and selective anti-AML activity, induces robust apoptosis, and produces an early reduction in MCL-1 protein signal. Its strong activity in FLT3-mutant AML models and substantially lower cytotoxicity in PBMCs and BJ fibroblasts suggest a favorable preliminary therapeutic window. Additional studies are warranted to define its mechanism of action and validate its selectivity across broader AML models.