Novel Metabolically Stable PCA-1/ALKBH3 Inhibitor Has Potent Antiproliferative Effects on DU145 Cells In Vivo

Anticancer Res. 2018 Jan;38(1):211-218. doi: 10.21873/anticanres.12210.


Novel potent prostate cancer antigen-1 (PCA-1)/alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (ALKBH3) inhibitors both in vivo and in vivo were designed and evaluated by a stability assay in an S9 mixture, a mixture of rat liver homogenate and co-factors, and oral absorbability assay in rat, as well as enzyme and cell assays, and resulted in the synthesis of a novel potent PCA-1/ALKBH3 inhibitor in vivo. Among them, compound 7l exhibited potent inhibitory activities in a xenograft model bearing DU145 tumor at 10 mg/kg by subcutaneous administration without negative side-effects. This inhibitory activity in vivo was more potent than that of HUHS015 at 32 mg/kg, a known PCA-1/ALKBH3 inhibitor, or docetaxel at 2.5 mg/kg, the drug clinically used for androgen-independent prostate cancer.

Keywords: Anti-prostate cancer drug; DU145; S9 mixture; anticancer drug; docetaxel; drug design; hepatic microsome; metabolic reaction; xenograft model.

MeSH terms

  • AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase / antagonists & inhibitors*
  • Animals
  • Antineoplastic Agents* / blood
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Burden / drug effects


  • Antineoplastic Agents
  • ALKBH3 protein, human
  • AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase