CCCP

555-60-2

C9H5ClN4

DMSO : >= 150 mg/mL (733.07 mM)

Immunology/Inflammation; Immunology/Inflammation; Metabolic Enzyme/Protease

CCCP inhibits STING-mediated IFN-beta production via disrupting mitochondrial membrane potential (MMP). CCCP inhibits activation of STING and its downstream signaling molecules, TBK1 and IRF3. IC50 & Target: STING^[1]
IFN-beta^[1] In Vitro: CCCP inhibits IFN-beta production induced by various types of the STING pathway activators. CCCP suppresses the phosphorylation of STING, TBK1, and IRF3 via disrupting the association of STING and TBK1. CCCP inhibits activation of STING and its downstream signaling molecules, TBK1 and IRF3, but not STING translocation to the perinuclear region. CCCP impairs the interaction between STING and TBK1 and concomitantly triggers mitochondria fission. Importantly, the knockout of the crucial mitochondria fission regulator Drp1 restored the STING activity, indicating that CCCP down-modulates the STING pathway through DRP1-mediated mitochondria fragmentation. The protonophore CCCP that disrupts membrane potential suppresses the DMXAA-triggered STING signaling pathway. CCCP drastically suppresses the production of IFN-beta in DMXAA-treated RAW264.7 cells and MEFs^[1]. In Vivo: The same dosage of 3?mg/kg.bw each of CCCP and PPEF is used. In both the cases 1?log reduction is observed in the bacterial load. However, when 3?mg/kg.bw of PPEF is used in combination with 3?mg/kg.bw of CCCP, 6 log₁₀ reduction is observed in the bacterial count. The developed model validates the enhanced antibacterial activity of combination therapy^[2].^99mTc-MIBI signals in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally) or vehicle is also measured. ^99mTc-MIBI signals decrease in rat hearts administered CCCP, and the ATP content, as measured by ³¹P magnetic resonance spectroscopy, decreased simultaneously. To investigate whether CCCP decreased the ^99mTc-MIBI signals in rats, we analyzed the radioisotope activity of excised heart tissue from rats administered CCCP. At 180 min after ^99mTc-MIBI injection, the ^99mTc-MIBI signals from the hearts in the CCCP group are significantly lower than those in the vehicle group^[3].