Activity tumor cells

Salinosporamides Salinispora tropica Inhibitors of proteasome function and cytotoxic activity (tumor cells)... 

IL-12 has been shown to exert striking therapeutic effects at nontoxic doses in mouse tumor models and in mouse models of a variety of infectious diseases and airway inflammation. In mouse tumor models, the therapeutic effects of IL-12 have been shown to result from its immu-noenhancmg activity, which requires both T cells and IFNy. In some models, administration of IL-12 can result in antiangiogenic effects, which may also contribute to its antitumor activity. Tumor cell-induced angiogenesis is... 

C-reactive protein Bactericidal activity Tumor cell killing Antigen-specific AFC Proliferation to ConA, PHA... 

A recent example of an anticancer antibody in development that functions via apoptosis is 1D09C3, a HuCAL-derived antibody specific for human leukocyte antigen (HLA)-DR [111, 112], which is highly expressed in B and T cell lymphomas. At the time of writing, this antibody is about to enter clinical trials for B cell lymphomas. The antibody causes cell killing selectively in activated tumor cells without the need for exogenous effector cells, via a mechanism that is caspase independent. 

The streptovaricins inhibit the reverse transcriptase of some RNA oncogenic vimses that may be involved in the process of viral transformation (see Antiviral agents). The atropisostreptovaricins again have similar activities to the corresponding natural isomers. The streptovals and streptovarone exhibit gready improved activity against reverse transcriptase relative to the streptovaricins (85), but their in vitro activities were low (86). The damavaricins also inhibit reverse transcriptase (4) as well as tumor cell growth (87). 

Fluorouracil (5-fluorouracil, 5-FU, Fig. 5) represents an early example of rational drag design in that it originated from the observation that tumor cells, especially from gut, incorporate radiolabeled uracil more efficiently into DNA than normal cells. 5-FU is a fluorinated pyrimidine analog that must be activated metabolically. In the cells 5-FU is converted to 5-fluoro-2>deoxyuridine-monophosphate (FdUMP). This metabolite inhibits thymidilate synthase which catalyses the conversion of uridylate (dUMP) to thymidilate (dTMP) whereby methylenetetrahydrofo-late plays the role of the carbon-donating cofactor. The reduced folate cofactor occupies an allosteric site of... 

Antineoplastic agents that cannot be grouped under subheadings 1-9 include miltefosine which is an alkylphosphocholine that is used to treat skin metastasis of breast cancer, and crispantase which breaks down asparagine to aspartic acid and ammonia. It is active against tumor cells that lack the enzyme asparaginase, such as acute lymphoblastic leukemia cells. Side effects include irritation of the skin in the case of miltefosine and anaphylactic reactions in the case of crispantase. Another recent development is the proteasome inhibitor bortezomib which is used to treat multiple myeloma. 

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