Year: 2013
Type: dissertation
Abstract: Signal Transducer and Activator of Transcription (Stat) 5 is a transcription factor that regulates the expression of genes involved in cell survival and proliferation. Hyper-activation of Stat5 is associated with several cancers. This work will discuss our efforts towards developing Stat5 inhibitors based on several scaffolds. One route we have explored involves modifying Stat3 inhibitors in order to produce selectivity for Stat5. The lead identified from this library shows nanomolar activity in vitro and induces leukemia cell death at 5 uM. We have also rigidified the core of the scaffold to improve selectivity. A library of compounds based on the resulting 1,4-benzodiazepine-2,5-dione structure were prepared. This presentation will also include our efforts to develop a new peptidomimetic scaffold based on a peptide sequence that binds to SH2 domains. By using a diverse set of novel scaffolds, we can generate small molecule inhibitors for the study and treatment of Stat5 induced cancers.
Source: TSpace (University of Toronto)
Author: Carla E. Brown
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2624991382