Preclinical Research BH3 mimetics are anticancer agents that reproduce the spatial arrangement of the BH3 domain of Bcl-2 family proteins. Just like the BH3-only proteins, these compounds bind to the hydrophobic cleft of the pro-survival Bcl-2 members such as Bcl-2 or Bcl-xL, and disrupt their heterodimerization with pro-apoptotic Bax or Bak, sensitizing cells to chemotherapy. In recent years, it has become clear that Bcl-2 family proteins are engaged in regulation of intracellular Ca2+ homeostasis, including Ca2+ release from the intracellular stores as well as Ca2+ fluxes across the plasma membrane. Given that BH3 mimetics shift the balance between the prosurvival and proapoptotic Bcl-2 members, they might indirectly exert effects on intracellular Ca2+ signals. Indeed, it has been reported that some BH3 mimetics release Ca2+ from the intracellular stores causing Ca2+ overload in the cytosol. Therefore, the effects of any new BH3 mimetics on cellular Ca2+ homeostasis should be tested before these compounds progress to clinical trials. Drug Dev Res 78 : 313-318, 2017. © 2017 Wiley Periodicals, Inc.
Keywords: BH3 mimetics; Bcl-2; calcium; cell signaling; clinical trials; protein-protein interaction.
© 2017 The Authors Drug Development Research Published by Wiley Periodicals, Inc.