There are over thirty nucleoside analogs that have been approved as drugs (by FDA and EMA) and several of these are on the WHO list over essential medicines. Most of these drugs are used as antivirals and in the treatment of cancer but they are also used for other indications like immunosuppression and as antiplatelet drugs. By targeting proteins involved in nucleotide metabolism we can improve the efficacy of current nucleoside treatments. One example of this strategy is the EMA approval in 2016 of the thymidine phosphorylase inhibitor tipiracil to improve trifluridine treatment of metastatic colorectal cancer. For example, we show targeting of SAMHD1 for improved efficacy of AraC treatments (Herold et al., 2017 Nature Medicine). Also, targeting nucleotide metabolism itself can prove highly effective as a mono-therapy based treatment, based on the aberrant metabolism in disease.
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