Gene-mediated enzyme prodrug therapy (GDEPT) seeks to increase the therapeutic index of anti-neoplastic agents by promoting selective activation of relatively nontoxic drug derivatives at sites of specific enzyme expression. Glucuronide prodrugs are attractive for GDEPT due to their low toxicity, bystander effect in the interstitial tumor space and the large range of possible glucuronide drug t...

Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies employed in the studies covered in this review were sorted by the type of drug synthesized into ester prodrugs, targ...

Tumor directed cytotoxic therapy is one of the major challenges for the success of chemotherapy. In order to accomplish this goal in neuroblastoma, we rationally designed a prodrug of etoposide as substrate for tyrosine hydroxylase, a well established neuroblastoma associated enzyme. Here, we report synthesis and characterization of a 3,4 dihydroxy-phenyl carbamate derivative of etoposide. In o...

Chemotherapeutic prodrugs have demonstrated success in killing cancer cells; however they also pose harm to healthy cells. The objective of this project was to synthesize an improved prodrug that is selectively activated only in the cancer microenvironment, thus minimally affecting healthy tissue. A photolabile linker was hypothesized to achieve said objective. The Yin group discovered that the...

PURPOSE This study was aimed to develop a novel Histidine-Leucine-Lopinavir (His-Leu-LPV) dipeptide prodrug and evaluate its potential for circumvention of P-gp and MRP2-mediated efflux of lopinavir (LPV) indicated for HIV-1 infection. METHODS His-Leu-LPV was synthesized following esterification of hydroxyl group of LPV and was identified by (1)H NMR and LCMS/MS techniques. Aqueous solubility...

Osteosarcoma (OS) is the most common primary malignant bone tumor in children, and microRNA-34a (miR-34a) replacement therapy represents a new treatment strategy. This study was to define the effectiveness and safety profiles of a novel bioengineered miR-34a prodrug in orthotopic OS xenograft tumor mouse model. Highly purified pre-miR-34a prodrug significantly inhibited the proliferation of hum...

A novel cancer targeting and pH-responsive prodrug was successfully designed and synthesized. This M-prodrug was demonstrated to have real-time drug release monitoring capability based on the concept of contact-mediated quenching between doxorubicin and a coumarin derivative.

Esterification of acetate with generic pharmaceutical compound has been commonly employed to produce ester prodrug for improving its potency when compared with the mother compound. Acetate, on the other hand, has been recognized to have inhibitory effect on the respiratory biochemistry. Here we demonstrate that acetate at a concentration of 400 microM exhibited significant growth inhibitory act...

Despite peptide transporter 1 (PEPT1) being responsible for the bioavailability for a variety of drugs, there has been little study of its potential involvement in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3 receptor agonist prodrug, utilizes PEPT1 to enhance absorption and bioavailability. In vitro studies were conducted to guide the decision to conduct a clini...