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Updated: Jul 5, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor

Christin Tse1, Alexander R Shoemaker, Jessica Adickes

  • 1Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6101, USA.

Cancer Research
|May 3, 2008
PubMed

Insights

ABT-263 is an orally bioavailable drug that inhibits Bcl-2 family proteins, inducing apoptosis and tumor regression. It shows promise as a single agent and in combination therapies for various cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Overexpression of prosurvival Bcl-2 family proteins (Bcl-2, Bcl-xL, Mcl-1) drives tumor growth and chemoresistance.
  • ABT-737, a Bcl-2 inhibitor, lacks oral bioavailability, limiting its therapeutic application.
  • There is a need for orally bioavailable inhibitors targeting Bcl-2 family proteins.

Purpose of the Study:

  • To report the biological properties of ABT-263, a novel, orally bioavailable Bcl-2 family inhibitor.
  • To evaluate the efficacy of ABT-263 as a single agent and in combination therapy in preclinical cancer models.

Main Methods:

  • ABT-263 was characterized as a Bad-like BH3 mimetic with high affinity for Bcl-2, Bcl-xL, and Bcl-w.
  • Oral bioavailability of ABT-263 was assessed in preclinical models.
  • The drug's mechanism of action, including disruption of Bcl-2 interactions and induction of apoptosis, was studied in human tumor cells.
  • Efficacy was evaluated in xenograft models of small-cell lung cancer, acute lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma.

Main Results:

  • ABT-263 demonstrated oral bioavailability of 20-50% in preclinical models.
  • The drug effectively disrupted Bcl-2/Bcl-xL interactions, leading to apoptosis initiation within 2 hours.
  • Single-agent oral administration of ABT-263 induced complete tumor regressions in small-cell lung cancer and acute lymphoblastic leukemia models.
  • ABT-263 significantly enhanced the efficacy of standard therapies in B-cell lymphoma and multiple myeloma models.

Conclusions:

  • ABT-263 is a potent, orally bioavailable BH3 mimetic with significant anti-cancer activity.
  • The drug's oral efficacy and ability to enhance combination regimens support its clinical development.
  • ABT-263 warrants clinical trials for small-cell lung cancer and B-cell malignancies, offering dosing flexibility.

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