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Small molecule toxins targeting tumor receptors

  1. Author:
    Dyba, M.
    Tarasova, N. I.
    Michejda, C. J.

  2. Author Address

    Michejda, CJ, POB B, Frederick, MD 21702 USA NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21702 USA.
    1. Year: 2004
  2. Journal: Current Pharmaceutical Design
    1. 10
    2. 19
    3. Pages: 2311-2334
  4. Type of Article: Review
  1. Abstract:

    Targeting toxic therapeutics to tumors through receptors Over expressed on file Surface of cancer cells can reduce systemic toxicity and increase the effectiveness of the targeted compounds. Small Molecule targeted therapeutics have a number of advantages over toxic immunoconjugates including, better tumor penetration, lack Of neutralizing host immune response and superior flexibility in selection of drug components with optimal specificity. potency and stability in circulation. Three major components of the targeted drug, the toxic warhead, tumor-specific ligand and the linker can influence the properties of each other and thus have to be optimized for each system. All receptor-targeted drugs are delivered inside the cells through endocytosis and undergo processing liberating the toxins in endosomes and lysosomes. Common delivery route defines a number of general requirements for each drug component. The review addresses currently known possible receptor targets and their ligands along with toxins that have been used and that have a potential to be successfully applied in tumor targeting. Linkers that are stable in Circulation, but efficiently cleaved in lysosomes constitute all essential component of receptor-targeted drugs and are evaluated in greater detail

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