Phase-specific drugs

The cytotoxic activity of cell cycle phase specific drugs (type II drugs) is time-dependent, and is different for cells in the sensitive phase (As) and in the resistant phase (Ar), as described as follows [2,27,28] ... 

Azathioprine is a phase-specific drug that is toxic to cells during nucleic acid synthesis. Phase-specific drugs are toxic during a specific phase of the mitotic cycle, usually the S-phase, when DNA synthesis is occurring, as opposed to cycle-specific drugs that kill both cycling and intermitotic cells. 

S-phase-specific drugs like adriamydn or M-phase-apedfic drugs like vincristine. it these possfoie hazards can be ruled out, a drug like PEu-I-aSP may represent a significant step ahead toward better tolerance of the enzyme. 

Reduction of cytotoxicity to normal tissue by new regimens of cell-cycle phase-specific drugs. Math. Biosci. 1988, 52... 

The desirability of attaining synchronisation of cell cycling to achieve maximum cell kill. For example, cells are killed or are arrested in mitosis by vincristine, which is then withdrawn. Cells then enter a new reproductive cycle more or less synchronously and when the majority are judged to be in a phase sensitive to a particular phase-specific drug, e.g. methotrexate or cytarabine, it is given. 

Table 1 Cell-cycle-phase-specific drugs...

Possibilities of using chemically modified enzymes with reduced immunogenicity have already been discussed above. However, before, for instance, PEG-l-ASP routinely enters clinical protocols, it must be clarified by randomized trials whether or not a G-phase-specific drug like 1-ASP interferes with... 

Drugs used to treat cancer act on some stage in the cell cycle, either on DNA synthesis or spindle formation or cause damage to preformed DNA. Phase-specific drugs act at a particular point in the cycle, usually S phase or M phase. Phase-non-specific drugs are cytotoxic at any point in the cell cycle and may be toxic to cancer cells in the... 

Mechloreth- amine Not phase-specific. Kills slow -growing tumors better than phase-specific drugs. Binds to N7 of guanine. Crosslinks DNA by binding to both strands. Decreased cellular uptake of drug and increased repair of drug-induced DNA damage. -... 

Aniicanccr drugs are classified according to their sites of action along the synthetic pathway of cellular macromolecules (top). Some drugs are only effective during part of the cell cycle (phase-specific drugs, left). 

Mitomycin C - Human sarcoma cells exposed to mitomycin C stimulated DNA synthesis in autochthonous lymphocytes. Preexposure of the tumor cells to autochthonous serum abrogated lymphocyte stimulation. 22 The use of mitomycin C in combination with cycle-phase specific drugs that may block cell repair, or with agents having a different mode of action has been suggested, 23 but preliminary combinations with phenylalanine mustardj and vincristine in the treatment of osteogenic sarcoma was without much... 

The stimulant urge-impulses are seusitive to euviroumeutal cues such as retumiug home aud associated multiple situatioual stimuli (e.g., paraphernalia, friends, etc.). With continued drug availability, it is not unusual to observe repetitious cycles of bingeing with intervening crash and intermediate withdrawal phases over a period of months. It is noted that conditioned withdrawal responses are less pronounced than with opiates yet, withdrawal appears to have a phase-specific relation to the reemergence of cue-sensitive responses that deserves further research. 

Sena G, Onado C, Cappella P, Montalenti F, Ubezio P. Measuring the complexity of cell cycle arrest and killing of drugs kinetics of phase-specific effects induced by taxol. Cytometry. 1999 Oct 1 37(2) 113-24. 

For anti-tumour drugs, Ozawa et cd. [27] proposed the following models. For cell cycle phase non-specific drugs (type I drug), the cytotoxic activity depends on the drug exposure, as reflected in the area under the intracellular concentration-time profile (AUC), and can be modelled using the following formula [2,28] ... 

Sensitivity and Specificity of Safety Assays should be Adjusted to the Phase of Drug Discovery... 

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