title: Therapeutic Agents Based on DNA Sequence Specific Binding.
abstract: DNA interactive agents have been used in the clinical setting for the treatment of cancer since the beginning of modern-era chemotherapy. Despite a shift of focus towards molecular targeted therapy, DNA remains a critical macromolecular target for anti-cancer intervention and the next generation of agents must conform to the optimum combination of increased therapeutic activity and reduced off-target toxicity. We evaluate the potential of non-covalent DNA binding small molecules as "gene-control" agents, exploiting inherent or engineered sequence selectivity, to target critical genomic sequences. In addition we review examples of natural products and synthetic derivatives that exert their activity through sequence specific DNA-covalent modification.
authors: Cancer Research UK Drug- DNA Interactions Research Group, UCL Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6BT, UK. luke.pett.12@ucl.ac.uk.
authors: Luke
authors: L
authors: Pett
authors: John A
authors: JA
authors: Hartley
authors: Konstantinos
authors: K
authors: Kiakos
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D013379:Substrate Specificity
chemical_list: D001688:Biological Products; D004273:DNA, Neoplasm