Therapeutic target modulation risk

GPCRs modulate a wide range of physiological processes and are implicated in numerous diseases. Therefore they form the largest class of therapeutic targets. G-protein coupled receptors represent the primary mechanism by which cells feel external environment and different stimuli, and pass the information to the interior of the cell. Abnormalities (usually by mutations but also by risk factors) of delicate balance in signaling mechanism often go to diseases and disorders, e.g. hypertension, hypertrophy, inflammatory diseases, cancer, fibrosis, diabetes, and diseases of central nervous system like Alzheimer disease. 

Figure 9-6 A generic strategy integrating the three facets of developmental toxicity risk assessment namely (a) the risk of pharmacologic modulation of the therapeutic target during gestation, (b) in silico, SAR and (c) in vitro screening. Abbreviations The chick embryo neural retina (CENR) embryonic stem cell test (EST), whole embryo culture (WEC), Good Laboratory Practice (GLP), Embryo/Fetal Developmental Toxicity (EFD) study. "Front-loading" is the conduct of the EFD study prior to Phase lib.

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