2. Academic Validation
  3. Design, synthesis and antitumor activity study of a gemcitabine prodrug conjugated with a HDAC6 inhibitor

Design, synthesis and antitumor activity study of a gemcitabine prodrug conjugated with a HDAC6 inhibitor

  • Bioorg Med Chem Lett. 2022 Sep 15;72:128881. doi: 10.1016/j.bmcl.2022.128881.
Yongliang Li 1,  Yuanpeng Liu 2,  Yiran Chen 3,  Kewei Wang 3,  Yepeng Luan 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Qingdao University Medical College, Qingdao University, Qingdao, Shandong, China; Department of Pharmacology, School of Pharmacology, Qingdao University Medical College, Qingdao University, Qingdao, Shandong, China.
  • 2 Department of Pharmacology, School of Basic Medicine, Qingdao University Medical College, Qingdao University, Qingdao, Shandong, China.
  • 3 Department of Pharmacology, School of Pharmacology, Qingdao University Medical College, Qingdao University, Qingdao, Shandong, China.
  • 4 Department of Medicinal Chemistry, School of Pharmacy, Qingdao University Medical College, Qingdao University, Qingdao, Shandong, China. Electronic address: luanqdu@sina.com.
PMID: 35810950 DOI: 10.1016/j.bmcl.2022.128881
Abstract

Gemcitabine, as a first-line antitumor drug, has attracted extensive attention. However the occurrence of drug resistance limits its clinical utilization. In this paper, a gemcitabine prodrug GZ was designed and synthesized by conjugation of gemcitabine with a newly reported HDAC6 selective inhibitor pentadecanoic acid. GZ displayed high cytotoxicity to nine Cancer cell lines with IC50 values in the low micromolar range. In vivo, GZ displayed superior antitumor activity to gemcitabine in a 4T1 tumor xenograft model without obvious pathological damage to important organs of mice. Our study showed that compound GZ is a potential gemcitabine prodrug, which is worthy of further antitumor activity exploration.

Keywords

Drug resistance; Gemcitabine; HDAC6; Pentadecanoic acid; Prodrug.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-150722
    HDAC6抑制剂
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