79648-88-7Relevant articles and documents
Synthesis, cleavage profile, and antitumor efficacy of an albumin-binding prodrug of methotrexate that is cleaved by plasmin and cathepsin B
Warnecke, Andre,Fichtner, Iduna,Sass, Gretel,Kratz, Felix
, p. 389 - 395 (2008/12/21)
Cathepsin B and plasmin are intra- or extracellular proteases that are overexpressed by several solid tumors. In order to exploit both proteases as molecular targets for tumor-specific cleavage of prodrugs, an albumin-binding formulation of methotrexate w
Tight binding ligand approach to oligosaccharide-grafted protein
Totani, Kiichiro,Matsuo, Ichiro,Ito, Yukishige
, p. 2285 - 2289 (2007/10/03)
A novel type of artificial glycoprotein was developed, by using dihydrofolate reductase (DHFR) and methotrexate (MTX) as a protein-ligand pair. Various oligosaccharides linked to MTX were shown to bind tightly with DHFR and afforded oligosaccharide-grafted protein, which could be isolated easily by lectin beads.
Synthesis of methotrexate-antibody conjugates by regiospecific coupling and assessment of drug and antitumor activities
Kralovec,Spencer,Blair,Mammen,Singh,Ghose
, p. 2426 - 2431 (2007/10/02)
In order to increase the retention of drug activity, regiospecific coupling has been used to synthesize conjugates of methotrexate (MTX, 1) with normal rabbit IgG (NRG) and a mouse anti-human renal cancer monoclonal IgG (Dal K-20). MTX γ-methyl ester (4) was produced either by selective esterification of MTX or by coupling of 4-amino-4-deoxy-N10-methylpteroic acid (2) with suitable glutamic acid derivatives. The MTX γ-methyl ester (4) was then converted to the corresponding hydrazide 6. An amide-linked conjugate was formed when the MTX γ-hydrazide (6) was converted to reactive acylating species 7 by using tert-butyl nitrite or trifluoroacetaldehyde, which were reacted with nucleophilic centers, presumably ε-amino groups, in native IgG. A hydrazone-linked conjugate was formed when MTX γ-hydrazide (6) was reacted directly with IgG that had first been oxidized with periodate to form polyaldehyde IgG. The regiospecifically synthesized conjugates were somewhat more effective inhibitors in vitro of dihydrofolate reductase and of colony formation by human renal cancer (Caki-1) cells than were control nonregiospecific conjugates.