AICA-riboside (acadesine), an activator of AMP-activated protein kinase with potential for application in hematologic malignancies

Van Den Neste, Eric;Van den Berghe, Georges;Bontemps, Françoise
(2010) Expert Opinion on Investigational Drugs : authoritative analysis of R&D trends — Vol. 19, n° 4, p. 571-578 (2010)

Files

32098.pdf
  • Restricted Access
  • Adobe PDF
  • 328.61 KB
Request a copy

Details

Authors
  • Van Den Neste, EricUCLouvain
    Author
  • Van den Berghe, GeorgesUCLouvain
    Author
  • Bontemps, FrançoiseUCLouvain
    Author
Abstract
IMPORTANCE OF THE FIELD: Despite considerable advances, B-cell chronic lymphocytic leukemia (CLL) is incurable with standard approaches. Thus, there remains a need for new therapies, particularly for patients who develop chemoresistance to DNA-targeting treatments. AICA-riboside (acadesine) is a nucleoside with a wide range of metabolic effects, including release of adenosine and activation of AMP-activated protein kinase (AMPK), which was initially developed as a cardioprotective agent. More recently, it has been shown that AICA-riboside induces apoptosis in various models of leukemia, including CLL. AREAS COVERED IN THIS REVIEW: The literature data show that apoptosis induced by AICA-riboside in CLL is not dependent on a functionally normal p53 pathway. Moreover, AICA-riboside is active towards resting and proliferative models of leukemia cells, including resistant phenotypes. Finally, studies in healthy subjects and during coronary artery bypass graft surgery show that AICA-riboside is devoid of serious toxicity. WHAT THE READER WILL GAIN: This paper reviews the mechanisms of action of AICA-riboside in normal and malignant cells and discusses how AICA-riboside could impact CLL treatment. TAKE HOME MESSAGE: We propose that AICA-riboside, which displays a relative selectivity and a favorable toxicity profile, may offer a new treatment option for CLL.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Van Den Neste, E., Van den Berghe, G., & Bontemps, F. (2010). AICA-riboside (acadesine), an activator of AMP-activated protein kinase with potential for application in hematologic malignancies. Expert Opinion on Investigational Drugs : authoritative analysis of R&D trends, 19(4), 571-578. https://doi.org/10.1517/13543781003703694 (Original work published 2010)