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Imaging cellular distribution of Bcl inhibitors using small molecule drug conjugates.

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.

SUBMITTER: Giedt RJ

PROVIDER: S-EPMC4240345 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Imaging cellular distribution of Bcl inhibitors using small molecule drug conjugates.

Giedt Randy J RJ Sprachman Melissa M MM Yang Katherine S KS Weissleder Ralph R

Bioconjugate chemistry 20141103 11

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. ...[more]

PMID: 25333750

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