Journal of Enzyme Inhibition and Medicinal Chemistry

Small Molecule Inhibitors for Targeting Cancer

Small molecule inhibitors remain one of the most dynamic and versatile classes of anticancer therapeutics and represent a cornerstone of modern precision oncology. Advances in structure-guided drug design, high-throughput screening, chemical biology, and computational modelling have enabled the rapid discovery of highly potent and selective modulators targeting oncogenic kinases, epigenetic enzymes, metabolic pathways, DNA-damage response nodes, and protein-protein interactions, which were once considered undruggable. The evolving landscape of cancer biology continues to reveal new molecular vulnerabilities, viz., covalent inhibitors, allosteric modulators, molecular glues, and PROTAC-inspired hybrid small molecules, which open unprecedented opportunities for designing next-generation inhibitors. This Article collection aims to highlight cutting-edge research in the discovery, conception, optimization, and molecular characterization of small-molecule therapeutics with improved potency, isoform specificity, addressing resistance, and optimal pharmacokinetic profiles. We welcome contributions spanning medicinal chemistry, hit-to-lead development, scaffold innovation, AI-guided target discovery and drug design, and translational pharmacology to advance the next wave of cancer-targeted small-molecule agents.

Cancer progression is driven by the dynamic interplay of genomic instability, metabolic reprogramming, immune escape, and the evolving tumor microenvironment. In this complex landscape, small-molecule inhibitors remain one of the most versatile therapeutic platforms, offering the ability to precisely modulate oncogenic enzymes, signalling networks, and protein-protein interactions. As resistance to current therapeutics intensifies, the demand for next-generation inhibitors that engage novel targets, exploit synthetic vulnerabilities, and reshape immune responsiveness has never been greater. Small molecules provide unique advantages in tunable physicochemical and pharmacokinetic properties, manufacturing scalability, and cost-effective development, which position them firmly at the forefront of future cancer therapeutics. Advances in bifunctional/hybrid modalities, targeted protein degraders, molecular glues, covalent chemistry, and structure-guided design are expanding the boundaries of what medicinal chemistry can achieve. By curating advances across these domains, this Collection seeks to accelerate discovery, foster interdisciplinary collaboration, and support the translation of molecular insights into clinically impactful therapies. Ultimately, driving innovation in small-molecule inhibitors is essential for delivering more precise, durable, and globally accessible cancer therapeutics.

This Article Collection presents a comprehensive examination of cutting-edge small-molecule strategies designed to modulate fundamental oncogenic processes. Manuscripts are invited that address advances in targeting kinase networks, epigenetic regulators, DNA-damage response pathways, immune modulation, inflammation, and other hallmarks of cancer central to its development and therapeutic resistance. The collection further welcomes studies on isoform-selective inhibitors and emerging bifunctional modalities, PROTACs based small molecule hybrids, and molecular glues, which expand the scope of druggable mechanisms. Detailed mechanistic explorations- encompassing structural characterization, biochemical interrogation, and molecular pathway analysis are particularly encouraged. By assembling high-quality research from medicinal chemistry, this collection aims to provide an authoritative resource that informs the design of next-generation anticancer therapeutics. This special edition invites original research articles and comprehensive reviews aligned with the theme of this collection and the journal's scope.

Proposed Subtopics (include, but are not limited to):

• Targeting Kinase networks
• DNA-damage response
• Immune modulation
• Inflammation in cancer
• Tumor microenvironment
• Epigenetic mechanisms
• Bifunctional modalities
• Isoform-selective inhibitors
• PROTACS
• Molecular glues
• Apoptosis and autophagy inducers
• Heat shock proteins

Please submit your manuscript on our website, using the promo code IENZ-2026-C41472 for 10% off the advertised article processing charge and selecting the corresponding Article Collection title in the drop-down menu through the submission process to indicate that your manuscript will be considered for the “Small Molecule Inhibitors for Targeting Cancer” Collection.

Please contact Haoyang Yi (Commissioning Editor) at [email protected] with any queries regarding this Article Collection.

Guest Advisor

Prof. Kunal Nepali

Kunal Nepali is an Associate Professor in the School of Pharmacy, Taipei Medical University, Taiwan. He has expertise spanning medicinal chemistry and organic synthesis with 15 years of experience in a broad range of drug development projects (mainly centered on cancer and gout). His research endeavors employ a rational structure-based drug design approach that lies at the interface of chemistry and biology to treat cellular processes via the logical design of therapeutics. Noteworthy to mention that Dr. Kunal was awarded Honorary Permanent Residency by the Government of Taiwan (Plum Blossom Card) in the year 2020 for his contributions to Science and Technology in Taiwan.