title: Identification of compounds that inhibit growth of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine-resistant cancer cells.
abstract: The dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) is a heterocyclic amine and is a common byproduct of cooked meat and fish. Although most cells undergo apoptosis when exposed to this mutagen, subsets develop resistance. Rather than die, these resistant cells persist and accumulate mutations, thereby driving tumorigenesis of exposed organs within the gastrointestinal tract. By applying a high-throughput cell-based screen of 32,000 small molecules, we have identified a family of compounds that specifically inhibit the growth of PhIP-resistant cancer cells. These compounds may prove useful for the treatment or prevention of gastrointestinal tumors arising after exposure to PhIP and related carcinogens.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. kbachman@som.umaryland.edu
authors.forename: Kurtis E
authors.initials: KE
authors.lastname: Bachman
authors.forename: Jason
authors.initials: J
authors.lastname: Sager
authors.forename: Ian
authors.initials: I
authors.lastname: Cheong
authors.forename: Marco
authors.initials: M
authors.lastname: Catto
authors.forename: Alberto
authors.initials: A
authors.lastname: Bardelli
authors.forename: Ben Ho
authors.initials: BH
authors.lastname: Park
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Angelo
authors.initials: A
authors.lastname: Carotti
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Christoph
authors.initials: C
authors.lastname: Lengauer
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007192:Indenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007192:Indenes; C504036:KLB-1 compound; D011724:Pyridazines; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine