Small Molecule Inhibitors: Design and Selection

Abstract

The discovery and optimization of small‐molecule inhibitors for the treatment of human disease has been the major focus of the pharmaceutical industry for more than a century. In the last decade, they have also attracted increased attention from academia because they provide a powerful means to interrogate biologic systems in an acute fashion. Although pharmaceutical companies have identified many small‐molecule inhibitors for drug targets, to find a desirable small‐molecule inhibitor for a specific target is still a major challenge for drug discovery and for chemical biology. Here, we present an overview of the computational approaches that can be exploited to discover small‐molecule inhibitors for protein targets of interest.

Dietary Oncopharmacognosy as a Crosswalk between Precision Oncology and Precision Nutrition

“…There is no doubt that this argument is true. However, it is also important to recognize that many first-generation drugs are also less specific and of lower affinity than their second-and third-generation successors, and that the drug development efforts have sometimes argued that this is a benefit relative to the development of drug resistance [62,90]. In many respects, this concern can be reduced to stoichiometry between pro-and anti-cancer effector molecules with an assessment of whether the effects of precision food patterns are sufficient to delay death from cancer such that other disease process account for mortality.…”

“…The drug development literature needs to be carefully mined for structure-activity relationships and to ensure that critical data about the pharmacological determinants of successful outcomes are available for examination. Standards for this purpose have been published, and the need to consider potential off-target effects has been emphasized [90,91].…”