Special Issue “Targeting of Functional Proteins in Disease Therapeutics: Enzyme Function and Inhibition Studies” - Editorial - Special Issue

Sep 30, 2026

Uploaded by Damian

Editorial introducing the Special Issue “Targeting of Functional Proteins in Disease Therapeutics: Enzyme Function and Inhibition Studies,” emphasizing recent advances in understanding enzyme function and inhibition. It highlights enzymes as pivotal drug targets across oncology, metabolic disorders, and neurodegeneration, and describes how structure-based design, high-throughput experimentation, and computational and AI-assisted modeling accelerate discovery, validation, and optimization. It also summarizes evolving inhibitor design strategies and provides an illustrative example of CRISPR/Cas9-based high-throughput screening of ASGR1 inhibitors validated by molecular and biochemical methods.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages4

Reading Time10 min

AccessFree to download

Editorial

Targeting functional proteins in disease therapeutics

Evolution of enzyme inhibitor design

Therapeutic landscape and screening technologies

Case example: CRISPR/Cas9 luciferase reporter for ASGR1

Structure-based and computational approaches

Applications across disease areas

Editorial Special Issue “Targeting of Functional Proteins in Disease Therapeutics: Enzyme Function and Inhibition Studies” Sung-Kun Kim Received: 3 December 2025 Accepted: 16 December 2025 Published: 21 December 2025 Copyright: © 2025 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Department of Natural Sciences, Northeastern State University, Tahlequah, OK 74464, USA; [kim03@nsuok.edu](kim03@nsuok.edu) We are delighted to introduce the collection Targeting of Functional Proteins in Disease Therapeutics: Enzyme Function and Inhibition Studies, which showcases recent advancesin understanding enzyme function and inhibition for disease treatment. Enzymes are often pivotal drug targets across oncology, metabolic disorders, and neurodegenerative conditions, with current strategies exploiting structure-based design, high-throughput experimental technologies, and computational modeling to improve the possibility of therapeutic innovation [1–3] . Additionally, enzymes are at the heart of cellular life, regulating processes ranging from metabolism to signaling, and orchestrating the complicated biochemical pathways that affect health and disease. Their roles and molecular specificity have made enzymes important targets for drug development, and recent progress in molecular biology, chemical synthesis, and computational science is radically transforming our ability to discover, validate, and optimize enzyme-targeted therapeutics [4] . Historically, targeting of enzymes has produced effective drugs for multiple diseases including infections, metabolic syndromes, and cancer. The rationale is that enzymes serve as biological switches, and their modulation can correct dysfunctional cellular states. Also, it should be mentioned that the landscape of targeting enzymes has evolved. The typical model of inhibitor design has given way to more sophisticated approaches, including allosteric modulation, covalent inhibition, and structure-based design that exploit the dynamic complexity of protein structures [5] . Recent surveys of FDA-approved therapeutics show that a large proportion of drugs—both small molecules and biologics—exert their action by targeting key enzymes or enzymelinked receptors [6] . Advances in high-throughput screening (HTS) and omics technologies have dramatically increased the scale and pace at which enzyme-inhibiting compounds can be discovered [7,8] . The synergy between biochemical assays, chemical informatics, and even AI-driven modeling is currently empowering scientists to tackle challenges of selectivity and efficacy that have historically limited the clinical use of enzyme inhibitors. The study by Gan et al. stands as a notable illustration of innovation in targeted enzyme therapeutics [1] . By leveraging CRISPR/Cas9 technology, the team established a luciferase reporter system in the HepG2 liver cell line to directly quantify the enzymatic activity of ASGR1, a receptor implicated in metabolism, liver disease, and cardiovascular health. High-throughput screening using this genetic model pinpointed promising inhibitors from microbial metabolite libraries, which were subsequently validated by molecular and biochemical methods. The approach reflects a broader trend wherein genetic engineering and omics are integrated with classical biochemistry to produce robust, physiologically relevant models for drug screening. Additionally, high-throughput platforms now enable the discovery not only of enzyme inhibitors but also of novel enzyme substrates, as seen in the exploration of glycosyltransferases and their role in detoxification and therapeutic modulation [3] . Mass spectrometric techniques have been adapted for rapid, accurate quantification of coenzymes such as NAD(H), offering powerful biomarkers for assessing disease states and treatment responses—especially in

FAQs

What is the focus of this Special Issue?

The Special Issue focuses on targeting functional proteins in disease therapeutics, specifically enzyme function and inhibition studies for improving disease treatment strategies.

How are enzymes positioned as drug targets across diseases?

The editorial states that enzymes are pivotal drug targets across oncology, metabolic disorders, and neurodegenerative conditions, with many approved therapeutics acting by targeting key enzymes or enzyme-linked receptors.

What example approach is used to identify enzyme inhibitors in the editorial?

It describes a CRISPR/Cas9-based luciferase reporter system in HepG2 cells to quantify ASGR1 enzymatic activity, followed by high-throughput screening to pinpoint inhibitors, then molecular and biochemical validation.

Sep 30, 2026

Uploaded by Damian