title: TMZ-BioShuttle--a reformulated temozolomide.
abstract: There is a large number of effective cytotoxic drugs whose side effect profile, efficacy, and long-term use in man are well understood and documented over decades of use in clinical routine e.g. in the treatment of recurrent glioblastoma multiforme (GBM) and the hormone-refractory prostate cancer (HRPC). Both cancers are insensitive against most chemotherapeutic interventions; they have low response rates and poor prognoses. Some cytotoxic agents can be significantly improved by using modern technology of drug delivery or formulation. We succeeded to enhance the pharmacologic potency with simultaneous reduction of unwanted adverse reactions of the highly efficient chemotherapeutic temozolomide (TMZ) as an example. The TMZ connection to transporter molecules (TMZ-BioShuttle) resulted in a much higher pharmacological effect in glioma cell lines while using reduced doses. This permits the conclusion that a suitable chemistry could realize the ligation of pharmacologically active, but sensitive and highly unstable pharmaceutical ingredients without functional deprivation. The re-formulation of TMZ to TMZ-BioShuttle achieved a nearly 10-fold potential of the established pharmaceutic TMZ far beyond the treatment of brain tumors cells and results in an attractive reformulated drug with enhanced therapeutic index.
authors.affiliation: German Cancer Research Center, Division of Biophysics of Macromolecules, INF 580, D-69120 Heidelberg, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Waldeck
authors.forename: Manfred
authors.initials: M
authors.lastname: Wiessler
authors.forename: Volker
authors.initials: V
authors.lastname: Ehemann
authors.forename: Ruediger
authors.initials: R
authors.lastname: Pipkorn
authors.forename: Herbert
authors.initials: H
authors.lastname: Spring
authors.forename: Juergen
authors.initials: J
authors.lastname: Debus
authors.forename: Bernd
authors.initials: B
authors.lastname: Didinger
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mueller
authors.forename: Joerg
authors.initials: J
authors.lastname: Langowski
authors.forename: Klaus
authors.initials: K
authors.lastname: Braun
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D020552:Comet Assay; D053938:DNA Fragmentation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D008297:Male; D019913:Nuclear Localization Signals / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000473:pathology; D000077204:Temozolomide; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002352:Carrier Proteins; D004337:Drug Carriers; D019913:Nuclear Localization Signals; D010446:Peptide Fragments; D003606:Dacarbazine; D000077204:Temozolomide
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