Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Apoptosis
-
Biological Transport
-
Boron Compounds / chemistry
-
Bridged Bicyclo Compounds, Heterocyclic / chemistry
-
Bridged Bicyclo Compounds, Heterocyclic / metabolism*
-
Bridged Bicyclo Compounds, Heterocyclic / pharmacology
-
Cell Line, Tumor
-
Fluorescent Dyes / chemistry
-
Fluorescent Dyes / metabolism*
-
Fluorescent Dyes / pharmacology
-
Humans
-
Intracellular Space / metabolism
-
Models, Molecular
-
Molecular Imaging / methods*
-
Protein Conformation
-
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
-
Proto-Oncogene Proteins c-bcl-2 / chemistry
-
Sulfonamides / chemistry
-
Sulfonamides / metabolism*
-
Sulfonamides / pharmacology
Substances
-
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
-
Boron Compounds
-
Bridged Bicyclo Compounds, Heterocyclic
-
Fluorescent Dyes
-
Proto-Oncogene Proteins c-bcl-2
-
Sulfonamides
-
venetoclax