Molecule anticancer drugs Small

Also nonkinase molecules might be important targets for anticancer drugs. For instance, the activity of the mitotic kinesin Eg5 (KSP, kinesin-5) can be inhibited by small molecules (e.g., monastrol, KSP-IA) resulting in mitotic defects associated with the induction of apoptosis. 

The overexpression of GSTs in some cancer cells, particularly of GST Pl-1, offers an opportunity to detect and treat some cancer types (e.g., ovarian cancer). Recent developments in the design of small molecules that either inhibit the catalytic activity of GST Pl-1 or use GST Pl-1 catalytic site to release the actual anticancer agent, have shown promising results in preclinical studies, with the graduation of 66 and 96 as potential anticancer drug candidates currently undergoing clinical trials. 

Application of molecular recognition principles allows the design of small molecules able to interact with biological systems for use, e.g. as anticancer drugs. 

Investigations of small molecules of biological interest by EXAFS include identification as to whether or not dimeric products of the anticancer drug cisplatin are formed before its interaction with DNA (Teo et al., 1978 Hitchcock et al., 1982) and determination of the fate of gold-based antiarthritic drugs which have been shown to be polymeric when absorbed into cells (Mazid et al., 1980). 

The anticancer drugs delivered by liposomes include many small molecule drugs such as DOX, daunoru-bicin, platinates, taxanes, camptothecin, etc. The most successful development is DOX-encapsulated pegylated liposomes, with a trade name of Doxil in the U.S. market or Cylax in the European market. Doxil has shown significant clinical advantages over free DOX and conventional DOX liposomes.f Enhanced tumor accumulation of Doxil has been demonstrated in numerous preclinical studies over a variety of tumor models. Similar effects were also observed in clinical uses. 

Attention has also been paid to the TSM detection of the interaction of surface-bound nucleic acids with small molecules such as specific-binding cis-and ra splatin anticancer drugs. The results showed two distinct kinetic processes that were interpreted in terms of nucleic acid binding of the hydrolysis products of the two drugs by Thompson and co-workers [54]. 

The rational design of active pharmaceutical compounds based on identification of genes involved in disease is demonstrated by the identification of compounds that stabilize the DNA binding domain of p53 in the active conformation. These small synthetic molecules not only promote the stability of wild-type p53 but also allowed mutant p53 to maintain an active conformation. A prototype compound caused the accumulation of conformationaUy active p53 in cells with mutant p53, enabling it to activate transcription and to slow tumor growth in mice. This class of compounds may thus be developed into anticancer drugs of broad utility. 

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