Abstract
Preparation of a novel c(RGDyK) targeted SN38 prodrug incorporating an indolequinone structure for bioreductively triggered drug release is described. This design yields a prodrug that targets surface molecules on tumor cells (alpha(v)beta(3) integrins) and releases drug under bioreductive conditions. There are three moieties in the prodrug design, namely a therapeutic drug SN38, an indolequinone structure serving as a drug releasing trigger, and an alpha(v)beta(3) integrin targeting peptide c(RGDyK). Preliminary studies showed that SN38 is released in the presence of a bioreductive enzyme (DT-diaphorase).
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Camptothecin / analogs & derivatives*
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Camptothecin / chemistry
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Camptothecin / metabolism
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Camptothecin / pharmacokinetics
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Female
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Humans
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Indolequinones / chemistry*
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Integrin alphaVbeta3 / antagonists & inhibitors
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Integrin alphaVbeta3 / metabolism*
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KB Cells
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Molecular Structure
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NAD(P)H Dehydrogenase (Quinone) / chemistry
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NAD(P)H Dehydrogenase (Quinone) / metabolism
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Oxidation-Reduction
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Peptides, Cyclic / chemistry*
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacokinetics*
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Structure-Activity Relationship
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Time Factors
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Uterine Cervical Neoplasms / chemistry
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Uterine Cervical Neoplasms / drug therapy*
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Uterine Cervical Neoplasms / metabolism
Substances
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Indolequinones
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Integrin alphaVbeta3
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Peptides, Cyclic
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Prodrugs
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SN38-Glu
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cyclo(Arg-Gly-Asp-Tyr-Lys)
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NAD(P)H Dehydrogenase (Quinone)
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Camptothecin