55383-37-4Relevant articles and documents
Absence of lysosomal cleavage in the cytotoxicity mechanism of an immunoconjugate composed of anti-α-fetoprotein monoclonal antibody and vindesine analog
Nagata, Shunji,Masuda, Kazuyoshi,Nogusa, Hideo,Hirano, Koichiro,Takagishi, Yasushi
, p. 480 - 483 (1996)
The effect of lysosomal enzyme inhibition on the cytotoxic activity of an immunoconjugate composed of anti-α-fetoprotein monoclonal antibody and vindesine analog (VDS) was studied in vitro using human tumor clonogenic assay (HTCA). Addition of the lysosome enzyme inhibitors, leupeptin and ammonium chloride, to the HTCA system had little influence on the cytotoxicity of this immunoconjugate. In separate experiments, no released VDS was detected by HPLC after incubation with the supernatant of rat liver homogenate without inhibitor. These results show that the immunoconjugate may bypass the lysosomal process and exert its activity as an intact or similar form.
Synthesis and biological analysis of prostate-specific membrane antigen-targeted anticancer prodrugs
Kularatne, Sumith A.,Venkatesh, Chelvam,Santhapuram, Hari-Krishna R.,Wang, Kevin,Vaitilingam, Balasubramanian,Henne, Walter A.,Low, Philip S.
, p. 7767 - 7777 (2010)
Ligand-targeted therapeutics have increased in prominence because of their potential for improved potency and reduced toxicity. However, with the advent of personalized medicine, a need for greater versatility in ligand-targeted drug design has emerged, w
CONJUGATES AND COMPOSITIONS FOR DRUG DELIVERY
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Paragraph 123, (2015/08/03)
The present invention provides folate receptor binding ligand‐drug delivery conjugates having the formula (F) nL1L2D. The conjugates have high affinity to folate receptor‐positive tumor cells and low toxicity for normal ce
Carbohydrate-based synthetic approach to control toxicity profiles of folate-drug conjugates
Vlahov, Iontcho R.,Santhapuram, Hari Krishna R.,You, Fei,Wang, Yu,Kleindl, Paul J.,Hahn, Spencer J.,Vaughn, Jeremy F.,Reno, Daniel S.,Leamon, Christopher P.
scheme or table, p. 3685 - 3691 (2010/08/22)
Figure presented To better regulate the biodistribution of the vinblastine-folate conjugate, EC145, a new folate-spacer that incorporates 1-amino-1-deoxy-d-glucitol-γ-glutamate subunits into a peptidic backbone, was synthesized. Synthesis of Fmoc-3,4;5,6-di-O-isopropylidene-1-amino-1-deoxy- d-glucitol-γ-glutamate 20, suitable for Fmoc-strategy solid-phase peptide synthesis (SPPS), was achieved in four steps from δ-gluconolactone. Addition of alternating glutamic acid and 20 moieties onto a cysteine-loaded resin, followed by the addition of folate, deprotection, and cleavage, resulted in the isolation of the new folate-spacer: Pte-γGlu-(Glu(1-amino-1-deoxy- d-glucitol)-Glu)2-Glu(1-amino-1-deoxy-d-glucitol)-Cys-OH (21). The addition of 21 to an appropriately modified desacetylvinblastine hydrazide (DAVLBH) resulted in a conjugate (25) with an improved therapeutic index. Treatment of 25 with DTT in neutral buffer at room temperature demonstrated that free DAVLBH would be released under the reductive environment of the internalized endosome.
