Folate-maytansinoids: target-selective drugs of low molecular weight

Int J Cancer. 1997 Dec 10;73(6):859-64. doi: 10.1002/(sici)1097-0215(19971210)73:6<859::aid-ijc16>3.0.co;2-#.

Abstract

Folate receptor is over-expressed in a variety of carcinomas. To design a cytotoxic drug that would selectively target these carcinomas, we synthesized folate-maytansinoids. These drugs showed high affinity toward folate receptor, appeared to enter cells exclusively via the folate receptor-mediated caveolar pathway and displayed high cytotoxic potency (in the range of 10[-11] to 10[-10] M) and remarkable selectivity for folate receptor-expressing carcinoma cell lines. Folate-maytansinoids represent a new class of tumor-specific agents in which the targeting and the cytotoxic function can be altered independently.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Carrier Proteins / metabolism
  • Drug Screening Assays, Antitumor
  • Fluorescent Antibody Technique, Indirect
  • Folate Receptors, GPI-Anchored
  • Humans
  • KB Cells
  • Maytansine / analogs & derivatives
  • Maytansine / chemical synthesis
  • Maytansine / metabolism
  • Maytansine / pharmacology*
  • Receptors, Cell Surface*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Receptors, Cell Surface
  • Maytansine