Prodrug-converting enzyme (PCE)

Prodrug-converting enzyme (PCE) is a functional classification for a diverse group of enzymes responsible for the metabolic activation of prodrugs into their active therapeutic forms (Rautio et al., 2008). This class includes various hydrolases such as Carboxylesterase 1 (CES1) and 2 (CES2), and Biphenyl hydrolase-like protein (BPHL), as well as oxidoreductases like Cytochrome P450 enzymes and transferases like Thymidine kinase (Shi et al., 2006; Kim et al., 2003). These enzymes play a critical role in modern pharmacology by enabling the use of prodrugs to overcome barriers such as poor solubility, low membrane permeability, or high systemic toxicity (Redinbo & Potter, 2005). In therapeutic contexts like Gene-Directed Enzyme Prodrug Therapy (GDEPT), specific non-human enzymes, such as bacterial cytosine deaminase, are introduced into tumor cells to locally activate prodrugs, thereby increasing the therapeutic index (Yang et al., 2011). Understanding the expression patterns and genetic variability of these enzymes is essential for predicting drug efficacy and avoiding adverse reactions, as seen with the variable activation of clopidogrel by CYP2C19 or irinotecan by CES2 (Mega et al., 2009; Humerickhouse et al., 2000).

Other names

Prodrug-activating enzyme (PAE)Prodrug-hydrolaseXenobiotic-metabolizing enzymeDrug-activating enzymeValacyclovir hydrolase (specifically for BPHL)Carboxylesterase (specifically for CES1/CES2)

Enzymatic conversion of an inactive prodrug into its pharmacologically active metabolite through chemical modifications such as hydrolysis, oxidation, reduction, or phosphorylation.