2. Academic Validation
  3. Bioevaluation of a dual PI3K/HDAC inhibitor for the treatment of diffuse large B-cell lymphoma

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.
Kehui Zhang 1,  Lei Huang 2,  Fangfang Lai 2,  Songwen Lin 1,  Hua Tian 1,  Deyu Wu 1,  Xiaoguang Chen 3,  Heng Xu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; CAMS Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
  • 2 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; CAMS Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
  • 3 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; CAMS Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: chxg@imm.ac.cn.
  • 4 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; CAMS Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: xuheng@imm.ac.cn.
PMID: 35644299 DOI: 10.1016/j.bmcl.2022.128825
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.

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