Identification of Ligands and Translation to Clinical Applications

Abstract

Technologic advances in molecular biology and biotechnology are increasingly being used for the development of new tumor-targeting tracers. In oncology, major progress has recently been achieved with peptidic and proteinaceous compounds. The development of new biocompatible molecules relies on the identification and validation of new target structures in close conjunction with the application of novel techniques. The identification of lead compounds by these techniques is followed by the screening of various derivatives of these molecules. Hence, high-throughput methods that generate vast libraries of epitopes have been applied. These libraries are screened to identify the few variants that bind with a high affinity to the target structure. A key feature of this strategy is the large number of candidate molecules that can be identified. Further evaluation and optimization of these molecules requires characterization of structure-function relationships and subsequent improvement with respect to binding, internalization, and biodistribution through a rational design of corresponding analogs.

Development of Folate Receptor−Targeted PET Radiopharmaceuticals for Tumor Imaging—A Bench-to-Bedside Journey

“…Finding a promising lead candidate for further investigation leading to clinical studies requires profound knowledge and a line of research and development in the fields of target identification, organic chemistry, radiochemistry, pharmacology and medical needs [85]. Key parameters to consider are high affinity and selectivity to the target, which must be high, choice of radionuclide, site of radiolabel, clearance and metabolism.…”

A Revisit to the Pretargeting Concept—A Target Conversion

“…Nevertheless, chances are such a small targeting molecule (or its target) may not be available. It is not easy to design a structure to provide both a high binding affinity to the tumor and a low normal tissue background simultaneously (Haberkorn et al, 2017; Kopka et al, 2017). Although most nuclear medicine imaging agents are small labeled molecules, few generate high target to non-tumor ratios and thus most are not satisfactory for tumor therapy (Herrmann et al, 2017; Bartholomä, 2018; Tsai and Wu, 2018).…”

“…The multiple-injections for pretargeting are apparently a disadvantage, but the high T/NT ratios are crucial for radiotherapy (Larson et al, 2015; Liu, 2016). Of course, if both an antibody and a small molecule are available for the same target, like the prostate membrane specific antigen (PMSA) (Smith-Jones et al, 2000, 2003; Sharkey, 2005; Haberkorn et al, 2017; Kopka et al, 2017), and the directly labeled small targeting molecule can achieve a similar success in terms of high T/NT ratios, it would be preferable to use that small molecule due to the single injection. However, in many cases antibody pretargeting and small targeting molecules are not comparable, because their primary targets are different.…”

Synthesis, Characterisation and in Silico Analysis of 4-(4- (Dimethylamino)phenyl)-6-Ethyl-1,3-Diphenylpiperidin 2-One as an Inhibitor of Colon Cancer

“…Hence, the synthesis of compounds with structure similar to the drugs in use is one of the area of research in pharmaceutical chemistry. [21][22][23]…”