Drug discovery using receptors that modulate gene expression.
Cytokines and non-peptidyl small molecules, such as steroid hormones, exert many of their effects on cells through rapid regulation of gene expression. This is achieved by the activation of different families of latent transcription factors, which bind to specific sequences in the promoters of regulated genes. High throughput assay systems have been developed based on a detailed molecular understanding of these transcriptional regulation processes, and are being used as screens for both agonists and antagonists of specific cytokines and hormones. The opportunities for the discovery of novel and selective compounds using these systems is discussed.
Lamb
P
P
Ligand Pharmaceuticals San Diego California 92121, USA.
Rosen
J
J
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D015195:Drug Design; D005786:Gene Expression Regulation; D006728:Hormones / Q000502:physiology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D018121:Receptors, Cytokine / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D004268:DNA-Binding Proteins; D006728:Hormones; D008024:Ligands; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases