CCCP | CAS#555-60-2 | Protonophore and uncoupler

MedKoo Cat#: 565494 | Name: CCCP

Description:

WARNING: This product is for research use only, not for human or veterinary use.

CCCP is a protonophore (h+ ionophore) and uncoupler of oxidative phosphorylation in mitochondria, inhibiting secretion of hepatic lipase and partially inhibiting the ph gradient-activated cl- uptake and cl-/cl- exchange activities in brush-border membrane vesicles

Chemical Structure

CCCP

CAS#555-60-2

Theoretical Analysis

MedKoo Cat#: 565494

Name: CCCP

CAS#: 555-60-2

Chemical Formula: C9H5ClN4

Exact Mass: 204.0203

Molecular Weight: 204.62

Elemental Analysis: C, 52.83; H, 2.46; Cl, 17.33; N, 27.38

Price and Availability

Size	Price	Availability
250mg	USD 350.00	2 Weeks
500mg	USD 550.00	2 Weeks
1g	USD 850.00	2 Weeks
2g	USD 1,350.00	2 Weeks
5g	USD 2,650.00	2 Weeks

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Related CAS #

555-60-2

Synonym

CCCP; Mesoxalonitrile 3-chlorophenylhydrazone;

IUPAC/Chemical Name

Carbonyl cyanide 3-chlorophenylhydrazone

InChi Key

UGTJLJZQQFGTJD-UHFFFAOYSA-N

InChi Code

InChI=1S/C9H5ClN4/c10-7-2-1-3-8(4-7)13-14-9(5-11)6-12/h1-4,13H

SMILES Code

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

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

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

In vitro activity:

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. Reference: Biochem Biophys Res Commun. 2017 Nov 4;493(1):737-743. https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(17)31704-7

In vivo activity:

(99m)Tc-MIBI signals were analyzed in Sprague-Dawley (SD) rat hearts perfused with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler known to reduce the mitochondrial membrane potential. (99m)Tc-MIBI signals could be used to detect changes in the mitochondrial membrane potential with sensitivity comparable to that obtained by two-photon laser microscopy with the cationic probe tetramethylrhodamine ethyl ester (TMRE). (99m)Tc-MIBI signals were also measured in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally) or vehicle. (99m)Tc-MIBI signals decreased in rat hearts administered CCCP, and the ATP content, as measured by (31)P magnetic resonance spectroscopy, decreased simultaneously. Next, (99m)Tc-MIBI was administered to Dahl salt-sensitive rats fed a high-salt diet, which leads to hypertension and heart failure. The (99m)Tc-MIBI signal per heart tissue weight was inversely correlated with heart weight, cardiac function, and the expression of atrial natriuretic factor, a marker of heart failure, and positively correlated with the accumulation of labeled fatty acid analog. The (99m)Tc-MIBI signal per liver tissue weight was lower than that per heart tissue weight. Reference: PLoS One. 2015 Jan 16;10(1):e0117091. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25594546/

	Solvent	mg/mL	mM
Solubility
	DMSO	41.0	200.37
	Ethanol	21.0	102.63

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 204.62 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Kwon D, Park E, Sesaki H, Kang SJ. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) suppresses STING-mediated DNA sensing pathway through inducing mitochondrial fission. Biochem Biophys Res Commun. 2017 Nov 4;493(1):737-743. doi: 10.1016/j.bbrc.2017.08.121. Epub 2017 Aug 30. PMID: 28859978.

In vivo protocol:

1. Kawamoto A, Kato T, Shioi T, Okuda J, Kawashima T, Tamaki Y, Niizuma S, Tanada Y, Takemura G, Narazaki M, Matsuda T, Kimura T. 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. doi: 10.1371/journal.pone.0117091. PMID: 25594546; PMCID: PMC4297193. 2. Sinha D, Pandey S, Singh R, Tiwari V, Sad K, Tandon V. Synergistic efficacy of Bisbenzimidazole and Carbonyl Cyanide 3-Chlorophenylhydrazone combination against MDR bacterial strains. Sci Rep. 2017 Mar 17;7:44419. doi: 10.1038/srep44419. PMID: 28303897; PMCID: PMC5355889.

1: Yamaguchi A, Ishikawa H, Furuoka M, Yokozeki M, Matsuda N, Tanimura S, Takeda K. Cleaved PGAM5 is released from mitochondria depending on proteasome-mediated rupture of the outer mitochondrial membrane during mitophagy. J Biochem. 2019 Jan 1;165(1):19-25. doi: 10.1093/jb/mvy077. PubMed PMID: 30247576. 2: Minanimo-Muta E, Kato T, Shioi T, Tanada Y, Kimura T. Cardiac effects of acute administration of a protonophore in a rat model. J Pharm Pharmacol. 2018 Sep;70(9):1209-1215. doi: 10.1111/jphp.12956. Epub 2018 Jun 25. PubMed PMID: 29943452. 3: Wauman J, Tavernier J. The intracellular domain of the leptin receptor prevents mitochondrial depolarization and mitophagy. Biochim Biophys Acta Mol Cell Res. 2018 Sep;1865(9):1312-1325. doi: 10.1016/j.bbamcr.2018.06.009. Epub 2018 Jun 19. PubMed PMID: 29932990. 4: Zhang X, Zhang Y, Wang F, Wang C, Chen L, Liu H, Lu H, Wen H, Zhou T. Unravelling mechanisms of nitrofurantoin resistance and epidemiological characteristics among Escherichia coli clinical isolates. Int J Antimicrob Agents. 2018 Aug;52(2):226-232. doi: 10.1016/j.ijantimicag.2018.04.021. Epub 2018 May 9. PubMed PMID: 29753133. 5: Stanford KR, Taylor-Clark TE. Mitochondrial modulation-induced activation of vagal sensory neuronal subsets by antimycin A, but not CCCP or rotenone, correlates with mitochondrial superoxide production. PLoS One. 2018 May 7;13(5):e0197106. doi: 10.1371/journal.pone.0197106. eCollection 2018. PubMed PMID: 29734380; PubMed Central PMCID: PMC5937758. 6: Wang YH, Li XN, Chen C, Zhang J, Wang GQ. Detection of floR gene and active efflux mechanism of Escherichia coli in Ningxia, China. Microb Pathog. 2018 Apr;117:310-314. doi: 10.1016/j.micpath.2018.02.042. Epub 2018 Feb 23. PubMed PMID: 29481973. 7: Setz C, Benischke AS, Pinho Ferreira Bento AC, Brand Y, Levano S, Paech F, Leitmeyer K, Bodmer D. Induction of mitophagy in the HEI-OC1 auditory cell line and activation of the Atg12/LC3 pathway in the organ of Corti. Hear Res. 2018 Apr;361:52-65. doi: 10.1016/j.heares.2018.01.003. Epub 2018 Jan 11. PubMed PMID: 29352609. 8: Kane MS, Paris A, Codron P, Cassereau J, Procaccio V, Lenaers G, Reynier P, Chevrollier A. Current mechanistic insights into the CCCP-induced cell survival response. Biochem Pharmacol. 2018 Feb;148:100-110. doi: 10.1016/j.bcp.2017.12.018. Epub 2017 Dec 22. Review. PubMed PMID: 29277693. 9: Park YS, Choi SE, Koh HC. PGAM5 regulates PINK1/Parkin-mediated mitophagy via DRP1 in CCCP-induced mitochondrial dysfunction. Toxicol Lett. 2018 Mar 1;284:120-128. doi: 10.1016/j.toxlet.2017.12.004. Epub 2017 Dec 11. PubMed PMID: 29241732. 10: Lombardo T, Folgar MG, Salaverry L, Rey-Roldán E, Alvarez EM, Carreras MC, Kornblihtt L, Blanco GA. Regulated Cell Death of Lymphoma Cells after Graded Mitochondrial Damage is Differentially Affected by Drugs Targeting Cell Stress Responses. Basic Clin Pharmacol Toxicol. 2018 May;122(5):489-500. doi: 10.1111/bcpt.12945. Epub 2018 Jan 3. PubMed PMID: 29205851. 11: Shimasaki K, Watanabe-Takahashi M, Umeda M, Funamoto S, Saito Y, Noguchi N, Kumagai K, Hanada K, Tsukahara F, Maru Y, Shibata N, Naito M, Nishikawa K. Pleckstrin homology domain of p210 BCR-ABL interacts with cardiolipin to regulate its mitochondrial translocation and subsequent mitophagy. Genes Cells. 2018 Jan;23(1):22-34. doi: 10.1111/gtc.12544. Epub 2017 Dec 5. PubMed PMID: 29205725. 12: Kansaku K, Takeo S, Itami N, Kin A, Shirasuna K, Kuwayama T, Iwata H. Maternal aging affects oocyte resilience to carbonyl cyanide-m-chlorophenylhydrazone -induced mitochondrial dysfunction in cows. PLoS One. 2017 Nov 28;12(11):e0188099. doi: 10.1371/journal.pone.0188099. eCollection 2017. PubMed PMID: 29182624; PubMed Central PMCID: PMC5705080. 13: Jarvi MP, Burton AJ. Adenylate control contributes to thermal acclimation of sugar maple fine-root respiration in experimentally warmed soil. Plant Cell Environ. 2018 Mar;41(3):504-516. doi: 10.1111/pce.13098. Epub 2017 Dec 11. PubMed PMID: 29124767. 14: Liang P, Rosas-Lemus M, Patel D, Fang X, Tuz K, Juárez O. Dynamic energy dependency of Chlamydia trachomatis on host cell metabolism during intracellular growth: Role of sodium-based energetics in chlamydial ATP generation. J Biol Chem. 2018 Jan 12;293(2):510-522. doi: 10.1074/jbc.M117.797209. Epub 2017 Nov 9. PubMed PMID: 29123027; PubMed Central PMCID: PMC5767857. 15: Khailova LS, Rokitskaya TI, Kotova EA, Antonenko YN. Effect of Cyanide on Mitochondrial Membrane Depolarization Induced by Uncouplers. Biochemistry (Mosc). 2017 Oct;82(10):1140-1146. doi: 10.1134/S0006297917100066. PubMed PMID: 29037134. 16: Xiao B, Deng X, Lim GGY, Xie S, Zhou ZD, Lim KL, Tan EK. Superoxide drives progression of Parkin/PINK1-dependent mitophagy following translocation of Parkin to mitochondria. Cell Death Dis. 2017 Oct 12;8(10):e3097. doi: 10.1038/cddis.2017.463. Erratum in: Cell Death Dis. 2018 Jul 19;9(8):794. PubMed PMID: 29022898; PubMed Central PMCID: PMC5680585. 17: Polo M, Alegre F, Moragrega AB, Gibellini L, Marti-Rodrigo A, Blas-Garcia A, Esplugues JV, Apostolova N. Lon protease: a novel mitochondrial matrix protein in the interconnection between drug-induced mitochondrial dysfunction and endoplasmic reticulum stress. Br J Pharmacol. 2017 Dec;174(23):4409-4429. doi: 10.1111/bph.14045. Epub 2017 Nov 7. PubMed PMID: 28940366; PubMed Central PMCID: PMC5715983. 18: Plášek J, Babuka D, Hoefer M. H(+) translocation by weak acid uncouplers is independent of H(+) electrochemical gradient. J Bioenerg Biomembr. 2017 Oct;49(5):391-397. doi: 10.1007/s10863-017-9724-x. Epub 2017 Sep 12. PubMed PMID: 28900787. 19: Dusane DH, Kyrouac D, Petersen I, Bushrow L, Calhoun JH, Granger JF, Phieffer LS, Stoodley P. Targeting intracellular Staphylococcus aureus to lower recurrence of orthopaedic infection. J Orthop Res. 2018 Apr;36(4):1086-1092. doi: 10.1002/jor.23723. Epub 2017 Oct 9. PubMed PMID: 28885721. 20: [In process]. Mikrobiologiia. 2016 Jul;85(4):481-483. PubMed PMID: 28853780.