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Histamine also upregulates NE

In particular, there have been many breakthroughs in the design of DON prodrugs, by modifying the carboxyl and amino groups of DON to obtain prodrugs that are not metabolized in plasma but decomposed in target cells, including acetyllysine substituted DON and JHU-083

doi: 10.1007/s11239-012-0759-x

This emanates from the fact that synthetic drugs are designed for just a purpose (for instance, treatment of a particular disease) and targeting a certain pathway and mechanism, while a large number of studies have revealed that naturally-occuring compounds are capable of affecting a wide variety of molecular signaling pathways (Guo et al., 2019