Multiple enzyme active sites

The term Multiple enzyme active sites refers to a pharmacological scenario where a single therapeutic agent interacts with the catalytic domains of several distinct enzymes, a phenomenon known as polypharmacology (Hopkins, A. L., Nature Chemical Biology, 2008). This is not a specific biological target but rather a descriptive classification for drugs that lack high selectivity, such as multi-kinase inhibitors or broad-spectrum anti-inflammatory agents (Guilherme, S. et al., Frontiers in Pharmacology, 2019). Drugs such as sunitinib or aspirin exemplify this approach by binding to various kinases or cyclooxygenases, respectively, to achieve their therapeutic effects.\n\nWhile targeting multiple enzymes can be a deliberate strategy to enhance efficacy in complex diseases like cancer or to prevent the development of drug resistance, it significantly increases the complexity of drug development (Anighoro, A. et al., Journal of Medicinal Chemistry, 2014). The primary challenge associated with this approach is the heightened risk of off-target effects and systemic toxicity, as the drug may interfere with essential metabolic or signaling pathways unrelated to the disease (Ramsay, R. R. et al., Clinical Pharmacology & Therapeutics, 2018). Consequently, this entry is considered an imprecise or incorrect designation for a specific molecular target in a therapeutic context.

Other names

Multi-targetPolypharmacologyNon-selective enzyme inhibition

Non-selective inhibition of multiple enzymatic catalytic domains