Figure 5.

A Mobius model of the gemcitabine model. Gemcitabine is a chemotherapeutic drug that is an analog of the normal cytidine that participates in transcription and in DNA replication. The pathway starts from the drug's intake by the cell and ends in its effect on cancerous cells resulting in cell death. The pathway shows cellular reactions that inactivate the drug and negative feedback of the drug's processing by the cell, which is inhibited by normal deoxycytidine triphosphate nucleotide (dCTP). The part of the PN that is shown in the figure represents transport of the cytidine or the drug analog into the cytoplasm, followed by two phosphorylation steps or inactivation of these molecules. At the bottom, the Petri Net branches into two paths: one for cytidine and one for the drug analog. dCTP downregulates the drug effect by inhibiting the first phosphorylation step of the drug (and cytidine). This is represented in the model by the rate of the phosphorylation1 reaction, which is proportional to the concentration of the phosphorylation substrate (Place19) and inversely proportional to the concentration of dCTP. The reactions are modeled as activities with exponential time distribution function.