CCCP is an oxidative phosphorylation (OXPHOS) uncoupler. CCCP induces activation of PINK1 leading to Parkin Ser65 phosphorylation^[1].

STING^[1]
IFN-β^[1]

CCCP inhibits IFN-β 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-β in DMXAA-treated RAW264.7 cells and MEFs^[1].
As low as 1 μM CCCP is enough to induce mitocytosis. In cells treated with 10 μM CCCP, which is the dose used for inducing mitophagy, mitocytosis is barely induced. Mechanistically, mitocytosis requires positioning of damaged mitochondria at the cell periphery, which occurs because damaged mitochondria avoid binding to inward motor proteins^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

204.62

C₉H₅ClN₄

555-60-2

Solid

Yellow to brown

N#C/C(C#N)=N/NC1=CC=CC(Cl)=C1

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Kwon D, et al. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) suppresses STING-mediated DNA sensing pathway through inducing mitochondrial fission. Biochem Biophys Res Commun. 2017 Aug 30. pii: S0006-291X(17)31704-7.  [Content Brief]

  [2]. Sinha D, et al. Synergistic efficacy of Bisbenzimidazole and Carbonyl Cyanide 3-Chlorophenylhydrazonecombination against MDR bacterial strains. Sci Rep. 2017 Mar 17;7:44419.  [Content Brief]

  [3]. Kawamoto A, et al. Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure. PLoS One. 2015 Jan 16;10(1):e0117091.  [Content Brief]

  [4]. Kondapalli C, et al. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol. 2012 May;2(5):120080.  [Content Brief]

  [5]. Haifeng Jiao, et al. Mitocytosis, a migrasome-mediated mitochondrial quality-control process. Cell. 2021 May 27;184(11):2896-2910.e13.  [Content Brief]