Bioevaluation of a dual PI3K/HDAC inhibitor for the treatment of diffuse large B-cell lymphoma

Bioorg Med Chem Lett. 2022 Sep 1:71:128825. doi: 10.1016/j.bmcl.2022.128825. Epub 2022 May 27.

Abstract

The synergistic anti-tumor effect by simultaneous inhibitions of PI3K and HDAC has been verified to provide the rationality of PI3K/HDAC dual inhibitors for cancer treatment. Notably, the outstanding effect of PI3K/HDAC dual inhibitors against DLBCL has been paid much attention, especially for RR-DLBCL. Our previously reported 4-methylquinazoine scaffold based PI3K/HDAC dual inhibitors could suppress the growth of solid tumors and hematologic malignancies both in vitro and in vivo, validating the potential as new therapeutic agents for cancer. In this research, we further investigated the anti-tumor activity of one of our compounds against DLBCL cell lines and in vivo zebrafish xenograft model as well as the underlying mechanism, hoping to provide a novel therapeutic agent for treating DLBCL.

Keywords: Cancer treatment; Diffuse large B-cell lymphoma; PI3K/HDAC dual inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Histone Deacetylase Inhibitors* / pharmacology
  • Histone Deacetylase Inhibitors* / therapeutic use
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / metabolism
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors / pharmacology
  • Xenograft Model Antitumor Assays
  • Zebrafish

Substances

  • Histone Deacetylase Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors