How to nurture natural products to create new therapeutics: Strategic innovations and molecule-to-medicinal insights into therapeutic advancements.

Natural products (NPs) are privileged structures interacting with biomacromolecular targets and exhibiting biological effects important for human health. In this review, we have presented NP-inspired strategic innovations that are promising for addressing preclinical and clinical challenges. An analysis of 'molecule-to-medicinal' properties for improvement of P3 and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles has been illustrated. The strategies include chemical evolution through knowledge of structure-medicinal properties, truncation of NPs to avoid molecular obesity, pseudo-NPs, selection of common structural features of NPs, medicinophore installation, scaffold hopping, and induced proximity. Molecule-to-medicinal property analysis can guide the development of 'nature-to-new' chemical therapeutics. Coupled with scientific advances and innovations in instrumentation, these strategies hold great potential for enhancing drug design and discovery.