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elevated stability in biomatrices, were found critical to method development and validation. The approach for the method development and validation provided a foundation for experiments that examine RK metabolism and bioavailability.Polymer-drug conjugates synthesized by binding therapeutic agents to functional polymers have long been a mainstay of prodrugs, while the slow drug release, insufficient efficacy of a single drug, and low selectivity hamper the clinical translation. By rational prodrug design, a targeted dual-acidity-labile po