Ecause , have predicted, there is no in vitro test to see if a new agent ZM-447439 sufficient selectivity t be of clinical benefit. Analog should be able to cells in vitro to kill, but to determine whether they are the corresponding anti-tumor selectivity t, the compound in vivo studies in mouse models for different types of cancer are evaluated. Since the selectivity of t for tumor cells is the most important aspect of a new anti-tumor agents in vitro and not the selectivity of t predict the new analogues was in tumor models in vivo as soon as we verify Possible. S well R, there are serious problems with the capacity t of the.
Currently used in vivo mouse model to clinical for the activity Cyclopamine T predict, but they are currently the best method for determining whether an agent antitumor activity of t at doses that are tolerated in an intact animal must be as big e amounts of connections are required for in vivo studies, the availability of connection is often a big obstacle to the achievement of these studies. However, the importance of should not be overestimated in vivo studies and should be performed as fast as the connection is sufficient to continue. Thanks langj Years of experience, in the process of drug development at Southern Research Institute, we have learned that the activity of t for a certain type of human tumor xenograft is not for activity t predict against this particular type of tumor in human disease. The best indicator of current clinical activity of t against each compound for each type of tumor is the presence of anti-tumor activity of t mice in many solid human tumor xenografts in M.
If an agent has anti-tumor activity of t at M Mice robust Parker Page 14 Chem Rev Author manuscript, increases available in PMC 2010 1 July proved. PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript NIH models and clinical studies are needed to the types of tumors, if any, are sensitively determined for the agents in humans. 5th Summary of purine and pyrimidine analogs are an important class of drugs in cancer treatment. Although these drugs share many structural and biochemical properties, each connection has a unique activity Th, which make it a useful drug. The basis of the selectivity of t of these agents is not clearly defined, but it is assumed that Haupt Chlich to differences in metabolism and proliferative between tumor cells and normal cells.
For example, the green is-Run deoxycytidine kinase expression Leuk Expected chemistry and lymphoma, the sensitivity of these tumors with nucleoside analogues, which are activated by this enzyme act. Additionally Tzlich are the most normal cells in a patient at rest and are therefore not sensitive to these agents. However, the selectivity of t of antimetabolites is still poor and better drugs with less toxicity ben t CONFIRMS. Analysis of existing agent identified three key features of the anti-metabolites, which are important for their F ability, abzut tumor cells th: Metabolism sufficiently active to its metabolite, long retention of the inhibition of metabolites and active, and actively supports DNA replication or function. The analog w re A reasonable substrate for the enzyme activation to be, although this aspect clearly from the T ACTION an analog can be influenced by the force of the active metabolite compared to the target enzyme. For example, an analog