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Keywords: : drug discovery, medicinal chemistry, phosphonate, prodrug activation, prodrugs Prodrugs have become increasingly common as replacements for drug candidates that have encountered obstacles during the development process

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This classical anti-mitotic drug binds soluble tubulin at colchicine site between - and -subunits, thus irreversibly forming tubulin-colchicine complexes, which induce many conformational changes in tubulin, disrupt further microtubule polymerization, and finally block mitosis at metaphase and induce cell death 50

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Lancet 2021;397(10278):97184