Molecular drug targets enzymes

Maeda H (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature the key role of tumor-selective macro-molecular drug targeting. Adv Enzyme Regul 41 189-207... 

The ideal molecular drug target is one which has been discovered in-house and is proprietary. Alternatively, a receptor or enzyme discovered by a researcher at a university, the cDNA of which is available for licensing by the drug company, could also provide an effective and proprietary target. These targets are often discovered serendip-itously, or could be the result of extensive fishing... 

The attractiveness of enzymes as drug targets results not only from the essentiality of their catalytic activity but also from the fact that enzymes, by their very nature, are highly amenable to inhibition by small molecular weight, drug-like molecules. Because of this susceptibility to inhibition by small molecule drugs,... 

Matrix metalloproteinases (MMPs) are a class of zinc- and calcium-dependent enzymes that are responsible for the metabolism of extracellular matrix proteins [27]. Increased activity of MMPs has been associated with pathological diseases such as arthritis, cancer, multiple sclerosis and Alzheimer s disease [28-31]. Therefore, they constitute an important group of drug targets. Their inhibition is accomplished by blocking the active site of the catalytic domain with ligands that contain hydroxamic or carboxylic acids to chelate the Zn metal. The identification of low molecular weight compounds that contain different scaffolds may lead to the development of a new class of specific inhibitors. 

The process of discovery of a new clinical candidate for a novel drug consists of several steps, which have to be iteratively repeated in order to obtain the structure of high potency with drug-like properties. The first and crucial for the whole project step is a choice of the proper molecular target of the drug — an enzyme or a molecular receptor. Then lead generation process and its subsequent optimization results in some candidates for clinical trials. 

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