1. Academic Validation
  2. Anti-Cancer Effects of CKD-581, a Potent Histone Deacetylase Inhibitor against Diffuse Large B-Cell Lymphoma

Anti-Cancer Effects of CKD-581, a Potent Histone Deacetylase Inhibitor against Diffuse Large B-Cell Lymphoma

  • Int J Mol Sci. 2020 Jun 19;21(12):4377. doi: 10.3390/ijms21124377.
Soo Jin Kim 1 2 U Ji Kim 2 Hae Yong Yoo 3 Yong June Choi 1 Keon Wook Kang 1
Affiliations

Affiliations

  • 1 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea.
  • 2 CKD Research Institution, Chong Kun Dang Pharmaceutical Corporation, Gyeonggi-do 16995, Korea.
  • 3 Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 08826, Korea.
Abstract

Double-hit lymphoma (DHL) and double-expressor lymphoma (DEL) are aggressive forms of lymphoma that require better treatments to improve patient outcomes. CKD-581 is a new histone deacetylase (HDAC) inhibitor that exhibited a better safety profile in clinical trials compared to Other HDAC inhibitors. Here, we demonstrate that CKD-581 inhibited the class I-II HDAC family via histone H3 and tubulin acetylation. CKD-581 treatment also up-regulated the phosphorylation of histone H2AX (γH2AX, DNA double-strand break marker), and reduced levels of MYC and anti-apoptotic proteins such as Bcl-2, BCL-6, BCL-XL, and Mcl-1 in DH/DE-diffuse large B cell lymphoma (DLBCL) cell lines. Ultimately, CKD-581 also induced Apoptosis via poly(ADP ribose) polymerase 1 (PARP1) cleavage. In a DLBCL SCID mouse xenograft model, CKD-581 exhibited anti-cancer effects comparable with those of rituximab (CD20 mAb). Our findings suggest that CKD-581 could be a good candidate for the treatment of DLBCL.

Keywords

CKD-581; MYC; diffuse large B cell lymphoma; histone deacetylase inhibitor.

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