Exploring the Anticancer Mechanism of Thienopyrazole Derivative Tpz-1 in Acute Myeloid Leukemia
Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drug’s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule organization. Additionally, structural analysis and medical text mining revealed a functional relationship between Tpz-1 and the understudied thienopyrazole chemical group. This dissertation therefore offers our colleagues in anticancer drug discovery an innovative methodology and class of molecules to drive future small molecule screening initiatives.
Biology|Cellular biology|Molecular biology|Oncology
Hess, Jessica Dyanne, "Exploring the Anticancer Mechanism of Thienopyrazole Derivative Tpz-1 in Acute Myeloid Leukemia" (2022). ETD Collection for University of Texas, El Paso. AAI29999447.