Small molecule anticancer agents

The small molecule anticancer agents are too numerous to describe individually in this chapter, but some representative molecules or classes are listed in Tables 1 and 2, and a few examples of those that have been associated with cardiovascular toxicity or other relevant target organ toxicities are described below. 

W.R Caron, K.R Morgan, B.A. Zamboni, and W.C. Zamboni, A review of study designs and outcomes of phase I clinical studies of nanoparticle agents compared with small-molecule anticancer agents, Clin Cancer Res, 19 (12), 3309-15, 2013. 

Small-Molecule Inhibitors of Glutathione S-Transferase PI-1 as Anticancer Therapeutic Agents... 

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. 

Selman Waksman s commitment to the isolation and screening of soil bacteria in the search for bioactive small molecules, especially potential antibiotics, was validated by the discovery of streptomycin. This led to the creation of the modem biopharmaceutical industry and the subsequent isolation of tens of thousands of bioactive small molecules from soil bacteria and other environments. A proportion of these compounds have become highly successfnl therapeutics, not only for all types of infectious diseases, but also in the treatment of many other human and animal ailments and as anticancer, immnno-modnlatory, and cardiovascular agents. Waksman and Fleming could be considered the fathers of chemical biology (Figure 1.1). 

Kerr, J. S., Slee, A. M., and Mousa, S. A. Small molecule alpha(v) integrin antagonists Novel anticancer agents. Exp. Opin. Invest. Drugs 9 1271-1279, 2000. 

M. Venkat Ram Reddy, born in 1967, received his Ph.D. in organic chemistry from the Indian Institute of Technology, Kanpur, India. Later, he worked with Nobel Laureate Professor Herbert C. Brown and Professor P. V. Ramachandran at the Department of Chemistry, Purdue University, for his postdoctoral studies. He was then appointed as the Assistant Research Scientist in the newly established Herbert C. Brown Center for Borane Research, Purdue University. Since Summer of 2004, he has been an Assistant Professor at the Departments of Pharmacy Practice and Pharmaceutical Sciences and Chemistry and Biochemistry, University of Minnesota Duluth. He has co-authored more than 60 publications and three patents. His research interests include asymmetric organic synthesis and synthesis of small molecules as anticancer agents. 

Small-molecule diaminopyrimidine derivatives were shown in 1948 to have an antifolate action. Subsequently, compounds were developed that were highly active against human cells (e.g. the use of methotrexate as an anticancer agent), protozoa... 

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