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[摘要]：Modulation of interactions between activated GPCRs (G-protein coupled receptors) and the intracellular (IC) signal transducers, heterotrimeric G-proteins, is an attractive, yet essentially unexplored, paradigm for treatment of certain diseases. Regulating downstream signaling for treatment of congenital diseases due to constitutively active GPCRs, as well as tumors where GPCRs are often overexpressed, requires the development of new methodologies. was developed to discover inhibitors that target the IC loops of activated GPCRs. As proof-of-concept, MEDSET developed and and transducin (Gt), its G-protein. A National Cancer Institute (NCI) compd. library was screened to identify compds. that bound at the interface between R* and its G-protein. High-scoring compds. from this virtual screen were obtained and tested exptl. for their ability to stabilize R* and prevent Gt from binding to R*. Several compds. that modulate signal transduction have been identified. |
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