Design, synthesis and antitumor activity of a novel PEG-A6-conjugated irinotecan derivative

Bioorg Med Chem Lett. 2020 Jan 15;30(2):126847. doi: 10.1016/j.bmcl.2019.126847. Epub 2019 Dec 3.

Abstract

A novel PEG-A6-conjugated irinotecan derivative 8 was designed and synthesized as antitumor agent by the PEGylation and A6-peptide modification of irinotecan. In vivo antitumor activity screening assay revealed that 8 exhibited better in vivo antiproliferation activity than irinotecan and its previous PEG-cRGD-conjugated derivative BGC0222 in MIA PaCa-2, NCI-H446, MDA-MB-231, HT-29 and NCI-N87 xenograft models, while the tumor of one in six mice in NCI-H446 assay and the tumors of two in six mice in MIA PaCa-2 assay completely subsided and disappeared within the 21-day period of 8-treatment, indicating that 8 should be a potential antitumor agent.

Keywords: In vivo antitumor activity; PEG-A6-conjugated irinotecan; Synthesis; Tumor regression; Tumor xenograft models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Irinotecan / chemical synthesis*
  • Irinotecan / chemistry
  • Mice
  • Molecular Structure
  • Xenograft Model Antitumor Assays

Substances

  • Irinotecan