37th Annual Student Research Conference
Inhibiting the KIX to c-Myb Interaction as a Potential Treatment for Leukemia
Zoe A. Vetter
Dr. Bill R. Miller, Faculty Mentor
c-Myb is a transcription factor protein essential for the proliferation and differentiation of hematopoietic cells. Recently, it was found that c-Myb expression is essential for the proliferation of leukemia cells and that partial inhibition of c-Myb can successfully eradicate leukemia cells without disrupting normal hematopoietic cell function, making it a promising drug target. The KIX domain of CBP (CREB binding protein) binds c-Myb and stimulates its transcriptional activity. Our research investigates small molecules that disrupt the interaction between c-Myb and KIX as a potential treatment for leukemia. 80 drug candidates from the ZINC12 database and 80 de novo generated ligands were computationally screened and then simulated using molecular dynamics (MD) to observe their behavior in the presence of KIX and c-Myb. Free energy calculations quantified the affinity of the ligands to the KIX/c-Myb complex, yielding two potential drugs that outperform previous drug candidates three-fold.
Keywords: Drug Design, Computational Chemistry, Leukemia, c-Myb
Topic(s):Chemistry
Biochemistry and Molecular Biology
Presentation Type: Oral Presentation
Session: 207-4
Location: MG 1000
Time: 11:15