Allosteric Inhibition of ABL Kinases: Therapeutic Potential in Cancer.

Journal Article (Journal Article;Review)

Tyrosine kinase inhibitors have revolutionized the world of cancer treatment in recent years, profoundly improving survival of patients with chronic myeloid leukemia (CML) and beyond. However, off-target toxicities of these inhibitors are well-described, and resistance has become a paramount concern. Novel allosteric inhibitors of the Abelson (ABL) family of tyrosine kinases, including GNF-2, GNF-5, and ABL-001, are equipped to overcome these issues. Several contemporary studies have demonstrated their potential efficacy in three key areas: primary hematologic and solid malignancies, metastasis, and combination with other small molecules. Further, ongoing clinical trials are investigating the efficacy of ABL-001 for the treatment of CML and recurrent solid tumors. This work reviews the current literature of the preclinical testing of GNF-2 and GNF-5 and the preclinical and clinical testing of ABL-001. Future research will continue to evaluate these promising inhibitors as both first-line therapy for solid tumors and salvage therapy when more traditional drugs such as imatinib fail.

Full Text

Duke Authors

Cited Authors

  • Jones, JK; Thompson, EM

Published Date

  • September 2020

Published In

Volume / Issue

  • 19 / 9

Start / End Page

  • 1763 - 1769

PubMed ID

  • 32606014

Pubmed Central ID

  • PMC7484003

Electronic International Standard Serial Number (EISSN)

  • 1538-8514

Digital Object Identifier (DOI)

  • 10.1158/1535-7163.MCT-20-0069


  • eng

Conference Location

  • United States