such as "Introduction", "Conclusion"..etc
Opportunistic cellular profiling is the preclinical corollaryto serendipitous clinical profiling, which led to discoveriessuch as Viagra’s use in erectile dysfunction (despiteits originally intended use in heart disease) or the demonstrationthat cholesterol synthesis inhibitors, statins, reduce CD69T cell antigen levels in T cells, which may extend the statin’sbenefits to immune regulation (33–35). As demonstratedhere, the ACP experiment identified PDGFR and c-kit as sideactivities for Glivec, which are under investigation for alternativetreatments of asthma and gastrointestinal stromal disorder (GIST).Similarly, the activities identified for the p38 kinase inhibitorBIRB796 and dual src/abl inhibitor BMS-354825 may prove usefulas tools to validate Tie2 and the Ephrins as drug targets inangiogenesis.
ACP profiling of molecular libraries against diverse cellularassays can be applied to many other problems as well. For example,it may be possible to identify novel ligands for whole panelsof orphan G-protein-coupled receptors by profiling collectionsof diverse lipid, metabolite, and neuropeptide hormone libraries.It may also be possible to identify combinations of drugs thatact synergistically against panels of patient-derived tumorcell lines. For pharmacogenomics, disease-associated SNPs identifiedby haplotype mapping can be engineered into SNP-dependent cellularassays and profiled against panels of preclinical drug candidatesto prospectively match patient variants with treatment. Theconfiguration of the ACP also allows screens for ligands withenhanced potency, selectivity, stability, or expression levelsfrom evolved protein libraries.
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