Conjugation of Dasatinib with MHI-148 Has a Significant Advantageous Effect in Viability Assays for Glioblastoma Cells

ChemMedChem. 2019 Sep 4;14(17):1575-1579. doi: 10.1002/cmdc.201900356. Epub 2019 Aug 7.

Abstract

We hypothesized that conjugation of the near-infrared dye MHI-148 with the anti-leukemia drug dasatinib might produce a potential theranostic for glioblastoma. In fact, the conjugate was found to bind the kinases Src and Lyn, and to inhibit the viability of a glioblastoma cell line with significantly greater potency than dasatinib alone, MHI-148 alone, or a mixture of dasatinib and MHI-148 at the same concentration. It was also used to successfully image a subcutaneous glioblastoma tumor in vivo.

Keywords: cancer; cyanine; glioblastoma; imaging agents; tumor targeting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / therapeutic use*
  • Carbocyanines / chemistry
  • Carbocyanines / therapeutic use*
  • Cell Line, Tumor
  • Dasatinib / chemical synthesis
  • Dasatinib / therapeutic use*
  • Drug Design
  • Female
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / therapeutic use*
  • Glioblastoma / drug therapy*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / therapeutic use*
  • Mice, Nude
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / therapeutic use*
  • Theranostic Nanomedicine / methods
  • Xenograft Model Antitumor Assays
  • src-Family Kinases / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Carbocyanines
  • Fluorescent Dyes
  • Indoles
  • MHI-148
  • Protein Kinase Inhibitors
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • Dasatinib