In vitro and in vivo pharmacokinetic and pharmacodynamic study of MBRI-001, a deuterium-substituted plinabulin derivative as a potent anti-cancer agent

Bioorg Med Chem. 2018 Sep 1;26(16):4687-4692. doi: 10.1016/j.bmc.2018.08.009. Epub 2018 Aug 4.


MBRI-001 was demonstrated preliminary better pharmacokinetics and antitumor effects than that of plinabulin in vivo. In this approach, we further carried out systematic pharmacokinetic and pharmacodynamic study of MBRI-001 in vitro and in vivo. MBRI-001 was tested stable in rat plasma and more stable in liver microsomes than plinabulin in vitro. In vivo, MBRI-001 could be distributed rapidly and widely in various tissues, especially the concentration of MBRI-001 in lung was remarkably higher than other tissues. Excretion study indicated that MBRI-001 might been decomposed and excreted as metabolites. Additionally, the combination treatment of MBRI-001 and gefitinib revealed better antitumor inhibition rate than monotherapy in vivo. Therefore, we suggest that MBRI-001 could be developed as a promising anti-cancer agent in near future.

Keywords: Anticancer agent; Combination treatment; MBRI-001; Pharmacodynamics; Pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Blood Proteins / chemistry
  • Blood Proteins / metabolism
  • Cell Line, Tumor
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism
  • Deuterium / chemistry
  • Diketopiperazines / chemistry*
  • Diketopiperazines / metabolism
  • Diketopiperazines / pharmacokinetics
  • Diketopiperazines / therapeutic use
  • Female
  • Half-Life
  • Humans
  • Inhibitory Concentration 50
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microsomes, Liver / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Tissue Distribution


  • Antineoplastic Agents
  • Blood Proteins
  • Diketopiperazines
  • NPI 2358
  • Cytochrome P-450 Enzyme System
  • Deuterium