Lich, and so little changes is the number of more desirable. Since all analogues of purines and pyrimidines used in cancer therapy are prodrugs, their mode of action is BTZ043 BTZ038 very complex and involves interaction with many anabolic and catabolic enzymes. Therefore, it will not be easy to replace this process with an empirical design process rational drug. Although the empirical approach, Parker Page 13 Chem Rev Author manuscript, increases available in PMC 2010 1 July. PA Author Manuscript NIH-PA Author Manuscript Author Manuscript NIH will use NIH-PA in the design of the new nucleosides is also a rational means of developing new drugs, new concepts of rational drug fa An optimum design involves the use of three-dimensional structure of the target protein associated with biochemical results and in silico modeling methodology.
This approach is particularly useful if a drug is largely but by acting on a single target enzyme. Although the structural information is used increasingly by the various enzymes that help to design new anti-metabolites, interact the design of new anti-metabolites not by a desire motivated by only one enzyme. For example, it is not be helpful to make a potent inhibitor of BMS-387032 nucleotides of the DNA polymerase based on structural information if the component con nucleotide-nucleoside inhibitor Ue can not easily into the cell, and triphosphate converted.
Nucleotide analogues are not good drugs because they are not easily penetrate cell membranes and phosphates quickly dissolved by plasma phosphatases deleted, Although have proved in recent years, nucleotide phosphonates in the treatment of certain diseases97 useful viral and some research groups to develop strategies provide for the nucleotides tumor cells.98 A further complicating factor in the rational design of new analogues, it is known that the drugs inhibit fter an intracellular Ren point of attack. This attribute can be used as a St Strength of this class of compounds and is one reason that anti-metabolites have been so successful in the clinic. The action points are more mechanistic, but to bring with them serious challenges in terms of rational drug design. As difficult as it is to develop a new drug that only intracellularly Ren inhibits target, it is much more than twice as difficult to inhibit a connection is able to create two or more enzymes.
The evaluation process of a new analogue of the antitumor activity of t is quite simple. When a new anti-metabolite was con U and synthesized, the first and most important experiment to determine whether the compound may in cancer cells in vitro assays to t Ten. A positive result indicates that the compound, the interaction with the metabolic enzymes of the other purine or pyrimidine path as a metabolite, an enzyme that create the DNA replication inhibited. Because of the betr Nocturnal knowledge of this class of compounds, k can The biochemical details of the mechanism of action with a good Ma based on accuracy on the knowledge of the structure of the new agents are outlined. However, biochemical studies are still needed to determine how the new agent structurally different Hnlichen connections, and if the new agent has the properties that can be useful k. B