Discovery of ursolic acid prodrug (NX-201): Pharmacokinetics and in vivo antitumor effects in PANC-1 pancreatic cancer

Bioorg Med Chem Lett. 2016 Nov 15;26(22):5524-5527. doi: 10.1016/j.bmcl.2016.10.008. Epub 2016 Oct 6.

Abstract

The aim of our study was to develop ursolic acid (UA) prodrugs in order to overcome UA's weakness, which has an extremely low bioavailability. UA-medoxomil (NX-201), one of our UA prodrugs, showed an improved bioavailability about 200times better than UA in rodent model. According to in vivo test performed with PANC-1 xenograft SCID mouse model, tumor growth rate decreased dose-dependently and 100mg/kg dose of NX-201 had an anticancer effect comparable to gemcitabine. Most of all the combination of NX-201 (50mg/kg, po, daily) and gemcitabine (40mg/kg, iv, 2timesperweek) even reduced tumor size after three weeks.

Keywords: Anticancer; Bioavailability; Pancreatic cancer; Prodrug; Ursolic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Humans
  • Mice, SCID
  • Pancreas / drug effects*
  • Pancreas / pathology
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Prodrugs / chemistry
  • Prodrugs / pharmacokinetics
  • Prodrugs / therapeutic use*
  • Triterpenes / chemistry
  • Triterpenes / pharmacokinetics
  • Triterpenes / therapeutic use*
  • Ursolic Acid
  • Xenograft Model Antitumor Assays

Substances

  • Prodrugs
  • Triterpenes