Folate-maytansinoids: target-selective drugs of low molecular weight.
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.
Ladino
C A
CA
ImmunoGen, Inc., Cambridge, MA 02139-4239, USA.
Chari
R V
RV
Bourret
L A
LA
Kedersha
N L
NL
Goldmacher
V S
VS
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D019084:Fluorescent Antibody Technique, Indirect; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D007624:KB Cells; D008453:Maytansine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011956:Receptors, Cell Surface; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D008453:Maytansine