Medicinal Chemistry Approaches in Oncology Drug Discovery

Andrey Colson^*
*Correspondence: Andrey Colson, Department of Technology of Chemical-Pharmaceutical and Cosmetic Substances, D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia, Email:

Introduction

Oncology drug discovery has witnessed remarkable progress driven by innovations in medicinal chemistry. The complexity of cancer biology demands precise, selective and potent agents that can disrupt malignant processes while sparing healthy cells. Medicinal chemists play a central role in designing such molecules by integrating structural biology, synthetic chemistry and pharmacokinetic optimization. The evolution of cancer therapeutics has moved from cytotoxic agents to targeted therapies and now to immuno-oncology and precision medicine. This shift has been enabled by advances in molecular modeling, high-throughput screening and biomarker-based drug design. As a result, medicinal chemistry continues to be the engine powering new and more effective cancer treatments [1].

Description

The foundation of oncology drug discovery lies in understanding the molecular drivers of tumorigenesis, such as mutations in kinases, oncogenes and tumor suppressors. Medicinal chemistry translates this knowledge into small molecules capable of modulating these targets. For Instance, Tyrosine Kinase Inhibitors (TKIs) such as imatinib and osimertinib have been developed through structure-guided design, showing how detailed knowledge of ATP-binding sites can lead to highly selective drugs. Beyond kinases, medicinal chemistry has also addressed epigenetic modulators, proteasome inhibitors and protein-protein interaction disruptors, expanding the druggable space in oncology. In recent years, covalent inhibitors have gained attention in cancer therapy due to their prolonged target engagement and potential to overcome resistance. Drugs like sotorasib, which targets KRAS G12C, exemplify this strategy. Additionally, fragment-based drug discovery and DNA-encoded libraries are emerging as powerful tools for identifying novel lead compounds with anti-cancer activity. These techniques offer the ability to explore vast chemical spaces and improve hit identification rates. Optimization of lead compounds involves not just potency but also favorable ADMET properties. Improving solubility, stability and oral bioavailability is essential for clinical success. For example, medicinal chemists utilize prodrug strategies, conformational constraints and bioisosteric replacements to fine-tune molecular properties [2].

The design of brain-penetrant molecules for glioblastoma or metastatic brain tumors presents additional challenges that require precise lipophilicity and transporter modulation. Another significant trend is the development of Antibody-Drug Conjugates (ADCs), where medicinal chemistry is key in linking cytotoxic warheads to monoclonal antibodies. The choice of linker chemistry, payload potency and release mechanisms are critical for therapeutic index and efficacy. Approved ADCs like trastuzumab emtansine and brentuximab vedotin illustrate the successful convergence of chemistry and immunotherapy. Immuno-oncology has also opened new avenues, with small molecules designed to modulate immune checkpoints, stimulate T-cell activity, or inhibit immunosuppressive enzymes like IDO1. Medicinal chemistry approaches have been instrumental in optimizing these agents for efficacy and safety. Furthermore, computational drug design, including AI-based modeling, is accelerating hit-to-lead cycles and improving predictive toxicology, streamlining the oncology pipeline. Oncology drug discovery remains one of the most challenging and dynamic areas in pharmaceutical research, with medicinal chemistry playing a central role in shaping therapeutic outcomes [3].

Medicinal chemistry approaches focus on optimizing molecular scaffolds, Structureâ??Activity Relationships (SAR) and physicochemical properties to improve potency, selectivity and pharmacokinetic behavior of anticancer agents. Key strategies in this domain include the design of small-molecule inhibitors targeting kinases, epigenetic regulators and proteinâ??protein interactions. The development of covalent inhibitors, fragment-based drug design and computer-aided drug discovery (CADD) tools has accelerated the identification of promising lead compounds. In addition, prodrug strategies and bioisosteric modifications are applied to enhance solubility, metabolic stability and tumor selectivity. These approaches enable medicinal chemists to overcome barriers such as multidrug resistance, off-target toxicity and limited bioavailability. Another critical aspect is the integration of medicinal chemistry with emerging therapeutic modalities. The chemical optimization of Antibodyâ??Drug Conjugates (ADCs), Proteolysis-Targeting Chimeras (PROTACs) and RNA-based therapeutics illustrates the versatility of chemistry in bridging traditional small molecules with biologics. Furthermore, nanomedicine platforms and targeted delivery systems are increasingly being combined with medicinal chemistry design to improve tumor penetration and reduce systemic toxicity [4-5].

Conclusion

Medicinal chemistry continues to be a cornerstone of oncology drug discovery, enabling the transformation of biological insights into life-saving treatments. Through innovative design strategies, precise target engagement and optimization of drug-like properties, chemists are addressing the multifaceted challenges of cancer. With the growing integration of omics data, AI tools and advanced screening technologies, the future of cancer drug discovery looks increasingly personalized and effective. Continued interdisciplinary collaboration will be vital to translate cutting-edge science into therapies that extend and improve the lives of cancer patients worldwide.

Acknowledgment

None.

Conflict of Interest

None.

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