Targets targeted therapeutics

VI. New Regulatory Challenges in Assessing the Use of Pharmacogenomic Diagnostics and the Use of Targeted Therapeutics... 

The identification of compounds with a desired property is a central pursuit in science. In the field of drug discovery combinatorial chemistry has played an increasingly important role for identification and optimization of drug leads which target therapeutically important biomolecules. For the successful implementation of combinatorial methods, new and innovative synthesis methods have been developed. Additionally, novel conceptual approaches to the design of compounds have been pursued to more efficiently generate libraries of small molecules. 

Biotechnology as a promising source of new and more efficient targeted therapeutics has been with us since the mid-1980s. While (as one should expect) some of the early promises have not quite been met, biotechnology has turned out to be a valuable source of new and valuable therapeutics. Table 12.1, summarizing the first 15 years of biologic approvals, demonstrates this (Malinowski, 1999 Maulik and Patel, 1997). 

Allen TM. Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2002 2 750. 

Reed JC. Dysregulation of apoptosis in cancer. J Clin Oncol 1999 17 2941-2953. Morisaki T, Katano M. Mitochondria-targeting therapeutic strategies for overcoming chemoresistance and progression of cancer. Curr Med Chem 2003 10(23) 2517-2521. 

Viruses essentially consist of genetic material (nucleic acids, green strands in (A) and a capsular envelope made up of proteins (blue hexagons), often with a coat (gray ring) of a phospholipid (PL) bilayer with embedded proteins (small blue bars). They lack a metabolic system but depend on the infected cell for their growth and replication. Targeted therapeutic suppression of viral replication requires selective inhibition of those metabolic processes that specifically serve viral replication in infected cells. 

The pre-clinical drug discovery process is typically a sequential selection and optimization process focusing, as summarized in Table 2, on different essential properties at each step. " Tool compounds required for early in vitro or in vivo target validation typically do not need to satisfy the same stringent in vivo efficacy and safety criteria as clinical candidates and drugs, which again depend on the targeted therapeutic indication. ... 

Molecular target distribution Toxicity potential increases if the molecular target is found in tissues other than what are targeted therapeutically... 

Wickstrom, E. (1992). Strategies for administering targeted therapeutic oligodeoxynucleotides. Trends Biotechnol. 10, 281-286. 

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