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Structure of CCG-4986.png
PubChem CID
ECHA InfoCard100.161.330 Edit this at Wikidata
Chemical and physical data
Molar mass374.819 g/mol
3D model (JSmol)

CCG-4986 is a drug which is the first non-peptide compound discovered that acts as a selective inhibitor of the Regulator of G protein signalling protein subtype RGS4.[1][2] Regulators of G protein signalling are proteins which act to limit and shorten the response produced inside a cell following activation of a G protein-coupled receptor. Since different RGS subtypes are expressed in different tissues and are associated with particular receptors, this makes it possible for selective inhibitors of RGS proteins to be developed, which should be able to enhance the activity of a particular receptor in a defined target tissue, but not elsewhere in the body.[3][4][5][6][7][8][9][10]


  1. ^ Roman DL, Talbot JN, Roof RA, Sunahara RK, Traynor JR, Neubig RR (January 2007). "Identification of small-molecule inhibitors of RGS4 using a high-throughput flow cytometry protein interaction assay". Molecular Pharmacology. 71 (1): 169–75. doi:10.1124/mol.106.028670. PMID 17012620.
  2. ^ Kimple AJ, Willard FS, Giguère PM, Johnston CA, Mocanu V, Siderovski DP (September 2007). "The RGS protein inhibitor CCG-4986 is a covalent modifier of the RGS4 Gα-interaction face". Biochimica et Biophysica Acta. 1774 (9): 1213–20. doi:10.1016/j.bbapap.2007.06.002. PMC 2084260. PMID 17660054.
  3. ^ Garzón J, Rodríguez-Muñoz M, de la Torre-Madrid E, Sánchez-Blázquez P (June 2005). "Effector antagonism by the regulators of G protein signalling (RGS) proteins causes desensitization of mu-opioid receptors in the CNS". Psychopharmacology. 180 (1): 1–11. doi:10.1007/s00213-005-2248-9. PMID 15830230.
  4. ^ Georgoussi Z, Leontiadis L, Mazarakou G, Merkouris M, Hyde K, Hamm H (June 2006). "Selective interactions between G protein subunits and RGS4 with the C-terminal domains of the mu- and delta-opioid receptors regulate opioid receptor signaling". Cellular Signalling. 18 (6): 771–82. doi:10.1016/j.cellsig.2005.07.003. PMID 16120478.
  5. ^ Hu W, Li F, Mahavadi S, Murthy KS (May 2008). "Interleukin-1beta up-regulates RGS4 through the canonical IKK2/IkappaBalpha/NF-kappaB pathway in rabbit colonic smooth muscle". The Biochemical Journal. 412 (1): 35–43. doi:10.1042/BJ20080042. PMC 3707494. PMID 18260825.
  6. ^ Paspalas CD, Selemon LD, Arnsten AF (January 2009). "Mapping the Regulator of G Protein Signaling 4 (RGS4): Presynaptic and Postsynaptic Substrates for Neuroregulation in Prefrontal Cortex". Cerebral Cortex. 19 (9): 2145–55. doi:10.1093/cercor/bhn235. PMC 2722426. PMID 19153107.
  7. ^ Prasad KM, Almasy L, Gur RC, Gur RE, Pogue-Geile M, Chowdari KV, Talkowski ME, Nimgaonkar VL (March 2009). "RGS4 Polymorphisms Associated With Variability of Cognitive Performance in a Family-Based Schizophrenia Sample". Schizophrenia Bulletin. 36 (5): 983–90. doi:10.1093/schbul/sbp002. PMC 2930339. PMID 19282471.
  8. ^ Hu W, Li F, Mahavadi S, Murthy KS (June 2009). "Upregulation of RGS4 expression by IL-1β in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by the PI3K/Akt/GSK3β pathway". American Journal of Physiology. Cell Physiology. 296 (6): C1310–20. doi:10.1152/ajpcell.00573.2008. PMC 2692422. PMID 19369446.
  9. ^ Leontiadis LJ, Papakonstantinou MP, Georgoussi Z (July 2009). "Regulator of G protein signaling 4 confers selectivity to specific G proteins to modulate mu- and delta-opioid receptor signaling". Cellular Signalling. 21 (7): 1218–28. doi:10.1016/j.cellsig.2009.03.013. PMID 19324084.
  10. ^ Song KS, Kim HJ, Kim K, Lee JG, Yoon JH (July 2009). "Regulator of G-protein signaling 4 suppresses LPS-induced MUC5AC overproduction in the airway". American Journal of Respiratory Cell and Molecular Biology. 41 (1): 40–9. doi:10.1165/rcmb.2008-0280OC. PMID 19059885.