ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development

J Hematol Oncol. 2015 Nov 20;8:129. doi: 10.1186/s13045-015-0224-3.

Abstract

With the advent of new agents targeting CD20, Bruton's tyrosine kinase, and phosphoinositol-3 kinase for chronic lymphoid leukemia (CLL), more treatment options exist than ever before. B-cell lymphoma-2 (BCL-2) plays a major role in cellular apoptosis and is a druggable target. Small molecule inhibitors of BCL-2 are in active clinical studies. ABT-199 (venetoclax, RG7601, GDC-0199) has been granted breakthrough designation by FDA for relapsed or refractory CLL with 17p deletion. In this review, we summarized the latest clinical development of ABT-199/venetoclax and other novel agents targeting the BCL-2 proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Humans
  • Leukemia, Lymphoid / drug therapy*
  • Leukemia, Lymphoid / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Tyrosine Kinases / drug effects*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use

Substances

  • Antineoplastic Agents
  • BCL2 protein, human
  • Bridged Bicyclo Compounds, Heterocyclic
  • Proto-Oncogene Proteins c-bcl-2
  • Sulfonamides
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • venetoclax