New multidrug-resistance-reversing drugs, MS-209 and SDZ PSC 833

Cancer Chemother Pharmacol. 1997;40 Suppl:S20-4. doi: 10.1007/s002800051056.

Abstract

The emergence of multidrug resistance (MDR) is a major problem in cancer chemotherapy. Many compounds have been developed to reverse MDR, and some of them are undergoing clinical trials. Among them, MS-209, a novel quinoline derivative, is one of the most potent MDR-reversing agents: MS-209 at 3 microM effectively reverses MDR in various cell lines in vitro. MS-209 directly interacts with P-glycoprotein (Pgp) and inhibits Pgp-mediated drug transport. Oral administration of MS-209 combined with anticancer drugs significantly increases the life span of mice bearing MDR tumor cells without causing serious side effects. SDZ PSC 833, a non-immunosuppressive analogue of cyclosporin A (CsA), is another potent MDR-reversing drug. Interestingly, the MDR-reversing activity of SDZ PSC 833 is enhanced in vitro and in vivo by MRK-16, a monoclonal antibody that recognizes an extracellular epitope of Pgp. Since MRK-16 promotes immune responses to MDR tumor cells expressing Pgp, the combined use of MRK-16, SDZ PSC 833, and antitumor drugs could be an effective therapeutic modality to reverse MDR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects
  • Cyclosporins / chemistry
  • Cyclosporins / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cyclosporins
  • Quinolines
  • dofequidar
  • valspodar