RT Journal Article SR Electronic T1 Small-molecule signal-transduction inhibitors: targeted therapeutic agents for single-gene disorders JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 145 OP 149 DO 10.1136/jmg.2008.064113 VO 47 IS 3 A1 Davies, D Mark A1 Sampson, Julian R YR 2010 UL http://jmg.bmj.com/content/47/3/145.abstract AB Mutations affecting over 2000 of the 20 000 or so genes in the human genome have been linked so far to specific inherited diseases, most of which are rare and have been poorly understood. Many of the genes involved encode components of intracellular signalling pathways that regulate processes such as the growth, proliferation, differentiation and survival or programmed death of cells during development and the maintenance of tissues and organs. Mutations that change the function of genes encoding signalling proteins thereby cause disorders ranging from birth defects to cancer. For Mendelian disorders, the essentially causal relationship between mutation and disease may present direct opportunities to therapeutically manipulate intracellular signalling. Here, we review recent examples of the use of small-molecule drugs to target components of signalling networks in single-gene disorders. We also consider the limitations of these “molecularly targeted” approaches and the difficulties in their clinical development as therapies for rare genetic diseases.