Identification of compounds that inhibit growth of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine-resistant cancer cells.
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.
Bachman
Kurtis E
KE
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. kbachman@som.umaryland.edu
Sager
Jason
J
Cheong
Ian
I
Catto
Marco
M
Bardelli
Alberto
A
Park
Ben Ho
BH
Vogelstein
Bert
B
Carotti
Angelo
A
Kinzler
Kenneth W
KW
Lengauer
Christoph
C
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
D000970:Antineoplastic Agents; D007093:Imidazoles; D007192:Indenes; C504036:KLB-1 compound; D011724:Pyridazines; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine