Protein substrates

Protein substrates are a broad category of proteins that serve as the targets for enzymatic modifications, such as phosphorylation by kinases, cleavage by proteases, or ubiquitination by the ubiquitin-proteasome system [1][2]. In the context of drug discovery and pharmacology, the term does not refer to a specific therapeutic target but rather to a functional designation for the molecules that are acted upon by enzymes, which are the primary targets of most drugs [3]. Many therapeutic agents, such as protease inhibitors and substrate-competitive kinase inhibitors, work by blocking the interaction between an enzyme and its specific protein substrates [3][4]. Because this term encompasses thousands of distinct proteins involved in virtually every biological process, it is considered an overly generic and non-specific entry for a drug target [1]. Identifying the specific substrates of a disease-relevant enzyme is essential for understanding the downstream effects of drug treatment and for developing biomarkers to monitor therapeutic efficacy [2]. Consequently, while protein substrates are fundamental to cellular signaling and homeostasis, the term itself is an incorrect classification for a single, actionable therapeutic target [1][3].

Other names

Enzyme substratesPolypeptide substratesDownstream effectorsTarget proteins

Not applicable for a generic category of molecules; however, drugs typically target the enzymes that modify these substrates via competitive inhibition or transition-state mimicry.