Methotrexate Carrier-Bound

Whiteley JM, Nimec Z, Galivan J. Treatment of reuber H35 hepatoma cells with carrier bound methotrexate. Mol Pharmacol 1981 19 505-508. 

Chu BCF, Howell SB. Differential toxicity of carrier-bound methotrexate toward human lymphocytes, marrow and tumor cells. Biochem Pharmacol 1981 30 2545-2552. 

D. D. N Da, E. W. Neuse and C. E. J. van Rensburg, Carrier-bound methotrexate. IV. Antiproliferative activity of polyaspartamide-MTX conjugates against leukemic lymphoblast cell lines. South Afr. J. Chem. -Suid-Afr. Tydskr. Chem., 59,135-140 (2006). 

The classic antifolate methotrexate MTX continues to be an important component of the chemotherapeutic armamentarium for a variety of cancers including pediatric ALL, osteogenic sarcoma, lymphoma, and breast cancer. Raltitrexed, another anti-folate, is used throughout much of the world outside of the United States for advanced colorectal cancer. Finally, Peme-trexed was approved in 2004 for the treatment of pleural mesothelioma and shortly thereafter as a second line treatment for nonsmall cell lung cancer. These drugs mimic the natural folate molecule and in so doing utilize the membrane-bound reduced folate carrier (RFC) protein system to gain entry into the cell. 

When the polymeric backbone is susceptible to hydrolysis, drug release may eventually result following degradation of the carrier. Ryser and Shen have shown that methotrexate (MTX) covalently bound to poly(L-lysine) (one molecule of drug per 27 lysyl residues) is able to impair the growth of a normally methotrexate — resistant Chinese hamster ovary cell line MTX-poly(L-Lys) is regarded as a lysosomotropic... 

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