abt-199 and 4-4-difluoro-4-bora-3a-4a-diaza-s-indacene

Overexpression of anti-apoptotic proteins such as Bcl-2 is a cellular mechanism to evade apoptosis; consequently, Bcl-2 inhibitors are being developed as anticancer agents. In this work, we have synthesized a fluorescent version of ABT-199 in an effort to visualize a drug surrogate by high resolution imaging. We show that this fluorescent conjugate has comparable Bcl-2 binding efficacy and cell line potency to the parent compound and can be used as an imaging agent in several cancer cell types. We anticipate that this agent will be a valuable tool for studying the single-cell distribution and pharmacokinetics of ABT-199 as well the broader group of BH3-mimetics.

Topics: Apoptosis; Biological Transport; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cell Line, Tumor; Fluorescent Dyes; Humans; Intracellular Space; Models, Molecular; Molecular Imaging; Protein Conformation; Proto-Oncogene Proteins c-bcl-2; Sulfonamides