1Laureate Institute of Pharmacy, Kathog, Jawalamukhi, Kangra, Himachal Pradesh, India
2School of Basic Medical Sciences, Faculty of Medicine, Kampus Perubatan, Universiti Sultan Zainal Abidin (UniSZA), 20400, Kuala Terengganu, Malaysia
3Exercise and Sports Science Programme, School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
4PEOPLE’S College of Dental Sciences and Research Centre, PEOPLE’s University, Madhya Pradesh, Bhopal, India
5Unit of Biochemistry, Faculty of Medicine, AIMST University, Bedong, Kedah, 08100, Malaysia
6Unit of Pharmaceutical Technology, Faculty of Pharmacy, AIMST University, Bedong, Kedah, 08100, Malaysia
7Unit of Physiology, Faculty of Medicine, AIMST University, Bedong-Kedah, 08100, Malaysia
*Corresponding Author E-mail: raousm@unisza.edu.my
Online Published on 29 July, 2025.
K. Barry Sharpless invented click chemistry in 2001, and it has revolutionized drug development with its effective, diverse, and selective chemical synthesis. In fact, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) process has become a crucial tool for drug-like particle assembly, functionalization of physiologically active mixtures, and accurate drug-biomolecule conjugation. Late-stage click chemistry applications span a number of industries, including prodrugs, antibody-drug conjugates (ADCs), and specific drug delivery systems including hydrogels and nanoparticles. Click reactions’ high specificity and bio-orthogonality have increased therapeutic precision, lessening side effects and improving therapeutic outcomes. New reactions, such as sulfur-fluoride exchange (SuFEx) and strain-promoted azide-alkyne cycloaddition (SPAAC), are a part of emerging trends in click chemistry that expand the range of applications. Click chemistry has improved lead compound synthesis, made it easier to develop pharmacophore linkers, and produced bio isosteres to improve drug potency and metabolic stability in the drug discovery process. The method’s role in creating cutting-edge treatments has also been highlighted by its contribution to the discovery of inhibitors for diseases like HIV, cancerous development, and bacterial infections. From early stage drug discovery to clinical development, click chemistry remains at the forefront of pharmaceutical analysis, highlighting its critical influence on ongoing drug development.
Click Chemistry, Drug Development, Trends, Applications, Copper(I)-Catalyzed Azide-Alkyne Cycloaddition, Antibody-Drug Conjugates, Strain-Promoted Azide-Alkyne Cycloaddition, Sulfur-Fluoride Exchange