Synthesis and evaluation of compounds that induce readthrough of premature termination codons

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5842-8. doi: 10.1016/j.bmcl.2011.07.107. Epub 2011 Aug 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia / drug therapy
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia / metabolism
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Codon, Nonsense / chemistry
  • Codon, Nonsense / genetics
  • Codon, Nonsense / metabolism*
  • Codon, Terminator / genetics
  • Codon, Terminator / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drug Design
  • Drug Evaluation, Preclinical*
  • Furans / chemical synthesis*
  • Furans / chemistry
  • Furans / pharmacology*
  • High-Throughput Screening Assays
  • Molecular Structure
  • Molecular Targeted Therapy
  • Mutation
  • Open Reading Frames
  • Peptide Chain Termination, Translational / genetics
  • Protein Biosynthesis / genetics
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / metabolism
  • Ribosomes / metabolism
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Transcriptional Activation
  • Tumor Suppressor Proteins / biosynthesis
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Codon, Nonsense
  • Codon, Terminator
  • DNA-Binding Proteins
  • Furans
  • RNA, Messenger
  • Thiazoles
  • Tumor Suppressor Proteins
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases