title: The synthesis of a c(RGDyK) targeted SN38 prodrug with an indolequinone structure for bioreductive drug release.
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).
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Baohua
authors.initials: B
authors.lastname: Huang
authors.forename: Ankur
authors.initials: A
authors.lastname: Desai
authors.forename: Shengzhuang
authors.initials: S
authors.lastname: Tang
authors.forename: Thommey P
authors.initials: TP
authors.lastname: Thomas
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D045563:Indolequinones / Q000737:chemistry*; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007624:KB Cells; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010456:Peptides, Cyclic / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D045563:Indolequinones; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D011355:Prodrugs; C106003:SN38-Glu; C550210:cyclo(Arg-Gly-Asp-Tyr-Lys); D016660:NAD(P)H Dehydrogenase (Quinone); D002166:Camptothecin