Related Experiment Video

Updated: Jun 8, 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

Discovery of a potent and selective Bcl-2 inhibitor using SAR by NMR

Andrew M Petros1, Jeffrey R Huth, Thorsten Oost

  • 1Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, United States.

Bioorganic & Medicinal Chemistry Letters
|September 28, 2010
PubMed

Insights

Researchers discovered a potent Bcl-2 inhibitor, a potential anti-cancer agent. This selective drug may overcome chemotherapy resistance and avoid side effects like thrombocytopenia.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Drug Discovery

Background:

  • The Bcl-2 protein family regulates apoptosis (programmed cell death).
  • Overexpression of anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-x(L), Mcl-1) confers cancer cell resistance to chemotherapy.
  • These anti-apoptotic proteins are critical targets for novel anti-cancer drug development.

Purpose of the Study:

  • To discover a potent and selective inhibitor of Bcl-2.
  • To identify a potential starting point for developing Bcl-2 selective anti-cancer therapeutics.
  • To address Bcl-x(L)-mediated thrombocytopenia side effects associated with existing agents like ABT-263.

Main Methods:

  • Structure-Activity Relationship (SAR) by Nuclear Magnetic Resonance (NMR) spectroscopy.
  • Structure-based drug design principles.
  • Inhibitor screening and characterization.

Main Results:

  • Discovery of a potent and highly selective Bcl-2 inhibitor.
  • The inhibitor's structure was elucidated and optimized.
  • The compound shows promise as a lead for developing targeted anti-cancer therapies.

Conclusions:

  • A novel, potent, and selective Bcl-2 inhibitor has been identified.
  • This discovery provides a foundation for developing new anti-cancer drugs targeting Bcl-2.
  • The developed agent may offer an improved therapeutic profile by avoiding Bcl-x(L)-related toxicities.

Related Concept Videos

Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...