![]() In the last three decades, with the advent of recombinant molecular biology technology and increased understanding of immunological mechanisms, the field has capitalized on these developments, resulting in a dramatic increase in the number of protein‐based therapeutics on the market. However, nature, in the form of the immune system, has developed a sophisticated and extraordinarily effective mechanism for producing long‐lived molecules with highly specific targeting properties. 2 Many of these small molecule therapeutics were designed to be highly specific to minimize the undesirable and unpredictable effects of off‐target interactions. Similarly, the disposition of drugs within the human body, that is the study of absorption, distribution, metabolism, and excretion (Pharmacokinetics) has been based primarily on small molecules. Pharmacologists developed the principles of drug action in the context of these products to understand their interactions with receptors, transporters, and enzymes (Pharmacodynamics). 1 In the last century, drugs were made by synthetic chemistry or purified from natural sources (eg, insulin). It has been said, somewhat facetiously, that pharmacology may be considered a branch of organic chemistry. Increased awareness of these advances may help to increase their use in exploratory research and further understand and characterize their pharmacological properties. Modifications to decrease the immunogenicity and increase the efficacy are described, with examples of optimizing their pharmacokinetic properties and enabling oral bioavailability. Monoclonal antibodies have several benefits, such as fewer off‐target adverse effects, fewer drug‐drug interactions, higher specificity, and potentially increased efficacy through targeted therapy. This review will discuss how the same basic principles can be applied to mAbs, with some important differences. ![]() The principles of pharmacology have enabled the development of high affinity, potent and selective small molecule therapeutics with reduced off‐target effects and drug‐drug interactions. Early therapeutic mAbs targeted soluble cytokines, but now that mAbs also target membrane‐bound receptors and have increased circulating half‐life, their pharmacology is more complex. However, their utilization as pharmacological tools in academic laboratories has lagged behind their small molecule counterparts. Thus, the therapeutic value and the elucidation of their pharmacological properties supporting clinical development of these large molecules are unquestioned. Over 100 monoclonal antibodies are in development, and their unique features ensure that these will remain a part of the therapeutic pipeline. The majority of mAb therapeutics are for oncological and immunological/infectious diseases, but these are expanding into other disease areas. In 2018, 12 new mAbs were approved by the FDA, representing 20% of the total number of approved drugs. ![]() To date, approximately 80 mAbs have been granted marketing approval. Monoclonal antibodies (mAbs) have emerged as a major class of therapeutic agents on the market.
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