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Overview
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Background
CCG-63808 is a selective inhibitor of RGS4 with IC50 value of 1.4 μM [1].RGS (regulators of G protein signaling) are multi-functional, GTPase-accelerating proteins and plays an important role in promoting GTP hydrolysis via heterotrimeric G proteins α subunit. RGS 4 is also known as RGP4 and plays a pivotal role in negatively regulating signaling upstream or at the level of the heterotrimeric G protein [2].CCG-63808 is a potent RGS4 inhibitor and is different from the reported RGS4 irreversibly inhibitor CCG-4986. Using the [32P] GTP single-turnover GAP assay, it was shown that CCG-63808 treatment inhibited GAP activity of RGS4 and the inhibition could be reversed by washing [1].
[1].Blazer, L.L., et al., Reversible, allosteric small-molecule inhibitors of regulator of G protein signaling proteins. Mol Pharmacol, 2010. 78(3): p. 524-33.
[2].Dobrivojevic, M., et al., Interaction between bradykinin and natriuretic peptides via RGS protein activation in HEK-293 cells. Am J Physiol Cell Physiol, 2012. 303(12): p. C1260-8.
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