Download MendeleyDiscovery and biological characterization of potent myeloid cell leukemia-1 inhibitors.
Lee, T., Bian, Z., Zhao, B., Hogdal, L.J., Sensintaffar, J.L., Goodwin, C.M., Belmar, J., Shaw, S., Tarr, J.C., Veerasamy, N., Matulis, S.M., Koss, B., Fischer, M.A., Arnold, A.L., Camper, D.V., Browning, C.F., Rossanese, O.W., Budhraja, A., Opferman, J., Boise, L.H., Savona, M.R., Letai, A., Olejniczak, E.T., Fesik, S.W.(2017) FEBS Lett 591: 240-251
- PubMed: 27878989
- DOI: https://doi.org/10.1002/1873-3468.12497
- Primary Citation of Related Structures:
5IEZ, 5IF4 - PubMed Abstract:
Myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that when overexpressed is associated with high tumor grade, poor survival, and resistance to chemotherapy. Mcl-1 is amplified in many human cancers, and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus, Mcl-1 is a promising cancer target. Here, we describe the discovery of picomolar Mcl-1 inhibitors that cause caspase activation, mitochondrial depolarization, and selective growth inhibition. These compounds represent valuable tools to study the role of Mcl-1 in cancer and serve as useful starting points for the discovery of clinically useful Mcl-1 inhibitors.
Organizational Affiliation:
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
