Folate‐maytansinoids: Target‐selective drugs of low molecular weight

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. Int. J. Cancer 73:859–864, 1997. © 1997 Wiley‐Liss, Inc.

Targeting Therapeutic and Imaging Agents to Folate Receptor Positive Tumors

“…This theory was in fact confirmed when FA was disulfide-linked to a synthetically modified ansamacrolide maytansine (DM1; Fig. (5b), Structure 8) [51]. The FA-DM1 conjugate was first shown to retain the specific affinity of FA towards the FR in a competitive binding assay, and immunofluorescence microscopy with an anti-maytansinoid mAb suggested that the FA-DM1 bound to KB cells and was then internalized into these FR-positive cells but not into FR-negative A375 cells.…”

Organometallic 99mTc-technetium(I)- and Re-rhenium(I)-folate derivatives for potential use in nuclear medicine

“…The well plates were pre-incubated at 37°C for 40 min. The solutions of the complexes 9b, 13b, 15b (25 ll, 1 MBq/ml), purified by HPLC, were added and the well plates incubated again at 37°C for 1 h and then rinsed three times with ice-cold PBS pH 7.4 or twice with PBS pH 7.4 and once with a stripping buffer (aqueous solution of 0.1 M acetic acid and 0.15 M NaCl), respectively, to remove bound complex from the FR on the cell surface [11]. The monolayers were dissolved in 1 N NaOH (1000 ll) and after transfer in 4 ml-tubes homogenized by vortex.…”

“…Several studies in recent years describe the derivatization of folic acid at the c-carboxyl group of the glutamate moiety [10]. To date folate conjugates of chemotherapeutic agents [11,12], antisense oligonucleotides and ribozymes [13,14], proteins and protein toxins [15][16][17], immunotherapeutic agents [18,19] as well as liposomes with entrapped drugs [20][21][22], plasmids [23][24][25] and radiopharmaceutical agents [10,[26][27][28] have been synthesized and successfully tested in cancer cells overexpressing the FR on their surface.…”

Electropolymerized Molecularly Imprinted Polymer Films of a Bis-Terthiophene Dendron: Folic Acid Quartz Crystal Microbalance Sensing

“…55 Folic acid is known to exhibit a high affinity to folate receptors (K d ≈ 1 Â 10 -10 mol/L), which makes it very attractive for targeting cytotoxic agents. 56,57 As a nutraceutical additive, folic acid is also routinely measured in food and biological samples. There is a need to monitor its concentration in fortified foods in compliance with government regulations and product monitoring.…”