title: Synthesis and evaluation of compounds that induce readthrough of premature termination codons.
abstract: A structure-activity relationship (SAR) study was carried out to identify novel, small molecular weight compounds which induce readthrough of premature termination codons. In particular, analogs of RTC13, 1, were evaluated. In addition, hypothesizing that these compounds exhibit their activity by binding to the ribosome, we prepared the hybrid analogs 13 containing pyrimidine bases and these also showed good readthrough activity.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, 405 Hilgard Ave., Los Angeles, CA 90095, United States. jung@chem.ucla.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Jung
authors.forename: Jin-Mo
authors.initials: JM
authors.lastname: Ku
authors.forename: Liutao
authors.initials: L
authors.lastname: Du
authors.forename: Hailiang
authors.initials: H
authors.lastname: Hu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gatti
mesh_terms: D001260:Ataxia Telangiectasia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018389:Codon, Nonsense / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018388:Codon, Terminator / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009154:Mutation; D016366:Open Reading Frames; D010443:Peptide Chain Termination, Translational / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D018388:Codon, Terminator; D004268:DNA-Binding Proteins; D005663:Furans; D012333:RNA, Messenger; D013844:Thiazoles; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases