Coumarins and precision medicine: Molecular mechanisms and pharmacogenomics in patient-specific therapeutic design

Coumarins represent a diverse class of natural and synthetic compounds with broad pharmacological relevance. Their variable efficacy and safety profiles across individuals highlight the need for precision-based therapeutic strategies that integrate molecular mechanisms with patient-specific factors. This review aims to critically evaluate the role of coumarins as model scaffolds in precision medicine, with emphasis on molecular targets, pharmacogenomic determinants, and patient-tailored therapeutic design. An integrative literature analysis was conducted encompassing molecular pharmacology, enzymatic and signaling pathway modulation, pharmacogenomics, population-specific genetic variability, adverse drug reactions, and emerging approaches for precision dosing, biomarker-guided therapy, and formulation strategies. Coumarins modulate multiple biological pathways through interactions with enzymes, transcription factors, and transporters involved in inflammation, cancer, metabolism, and cardiovascular regulation. Genetic variability in key metabolic and target genes, including cytochrome P450 isoforms and vitamin K cycle components, significantly influences efficacy, dosing requirements, and toxicity. Notably, Cytochrome P450 2C9 (CYP2C9) and Vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphisms were consistently associated with altered warfarin sensitivity across populations, while osthole and bergapten demonstrated pathway-specific modulation of Nuclear factor kappa B (NF-κB) and Signal transducer and activator of transcription 3 (STAT3) signaling, respectively. Advances in pharmacogenomics, biomarker identification, and drug–drug interaction management enable individualized coumarin therapy, while novel delivery systems further enhance therapeutic precision. Coumarins provide a compelling framework for implementing precision medicine principles in both synthetic and natural product-based therapies. Integrating molecular mechanisms with pharmacogenomic and clinical data can improve safety, optimize efficacy, and support rational patient-specific treatment strategies, although further translational and real-world validation remains essential. • Coumarins serve as versatile scaffolds for precision medicine applications. • Genetic variability critically affects coumarin efficacy, safety, and dose requirements. • Pharmacogenomics enables genotype-guided dosing to reduce adverse drug reactions. • Biomarker-informed strategies support patient-specific coumarin therapy selection. • Integration of real-world and clinical data facilitates the translation of coumarin precision therapy into practice.