Diphenyleneiodonium chlorideGPR3 agonist CAS# 4673-26-1 |
- A-867744
Catalog No.:BCC1324
CAS No.:1000279-69-5
- Rocuronium Bromide
Catalog No.:BCC1068
CAS No.:119302-91-9
- Rivastigmine
Catalog No.:BCC1900
CAS No.:123441-03-2
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 4673-26-1 | SDF | Download SDF |
PubChem ID | 2733504 | Appearance | Powder |
Formula | C12H8ClI | M.Wt | 314.55 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | DPI | ||
Solubility | Soluble to 10 mM in DMSO | ||
SMILES | C1=CC=C2C(=C1)C3=CC=CC=C3[I+]2.[Cl-] | ||
Standard InChIKey | FCFZKAVCDNTYID-UHFFFAOYSA-M | ||
Standard InChI | InChI=1S/C12H8I.ClH/c1-3-7-11-9(5-1)10-6-2-4-8-12(10)13-11;/h1-8H;1H/q+1;/p-1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | GPR3 agonist (EC50 = 1 μM); activates adenylate cyclase through GPR3 but not GPR6 or GPR12. Also induces Ca2+ mobilization and β-arrestin receptor internalization. Binds strongly to flavoproteins; inhibits several enzymes, including NO synthase, NADPH oxidases and NADPH cytochrome P450 oxidoreductase. Also inhibits platelet aggregation. |
Diphenyleneiodonium chloride Dilution Calculator
Diphenyleneiodonium chloride Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 3.1791 mL | 15.8957 mL | 31.7914 mL | 63.5829 mL | 79.4786 mL |
5 mM | 0.6358 mL | 3.1791 mL | 6.3583 mL | 12.7166 mL | 15.8957 mL |
10 mM | 0.3179 mL | 1.5896 mL | 3.1791 mL | 6.3583 mL | 7.9479 mL |
50 mM | 0.0636 mL | 0.3179 mL | 0.6358 mL | 1.2717 mL | 1.5896 mL |
100 mM | 0.0318 mL | 0.159 mL | 0.3179 mL | 0.6358 mL | 0.7948 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
Diphenyleneiodonium chloride (DPI) is an agonist of GPR3 with EC50 value of 1μM [1]. Also, diphenyleneiodonium chloride inhibits NADH oxidase (NOX), NO synthase and cytochrome P450 reductase [2] [3] [4].
G protein-coupled receptor 3 (GPR3) is an orphan G protein-coupled receptor (GPCR) with constitutive G(s) signaling activity that activates cyclic AMP and is mainly expressed in mammalian brain and oocytes [1].
DPI is a GPR3 agonist. In HEK293 cells stably expressed GPR3, DPI increased the level of intracellular cAMP, which was independent of NOX inhibition. DPI activated adenylate cyclase in cells expressing GPR3. In HeLa cells coexpressed β-arrestin2 and GPR3, DPI increased Ca2+ mobilization, GPR3 receptor desensitization and membrane localization of β-arrestin2 [1]. In HeLa cells, DPI inhibited NADPH oxidation by NOX with EC50 value of 0.1 μM [2]. In mouse macrophages, DPI irreversibly and completely inhibited NO synthase, which was blocked by NADP+, NADPH or 2’ 5’ -ADP. Also, DPI inhibited acetylcholine-induced relaxation of norepinephrine-preconstricted rabbit aortic rings with IC50 value of 300 nM [3]. DPI irreversibly inhibited NADPH cytochrome P450 oxidoreductase with Ki value of 2.8 μM [4].
In rats, DPI (10-5 mol/kg) inhibited the depressor response to acetylcholine [5].
References:
[1]. Ye C, Zhang Z, Wang Z, et al. Identification of a novel small-molecule agonist for human G protein-coupled receptor 3. J Pharmacol Exp Ther, 2014, 349(3): 437-443.
[2]. Morré DJ. Preferential inhibition of the plasma membrane NADH oxidase (NOX) activity by diphenyleneiodonium chloride with NADPH as donor. Antioxid Redox Signal, 2002, 4(1): 207-212.
[3]. Stuehr DJ, Fasehun OA, Kwon NS, et al. Inhibition of macrophage and endothelial cell nitric oxide synthase by diphenyleneiodonium and its analogs. FASEB J, 1991, 5(1): 98-103.
[4]. Tew DG. Inhibition of cytochrome P450 reductase by the diphenyliodonium cation. Kinetic analysis and covalent modifications. Biochemistry, 1993, 32(38): 10209-10215.
[5]. Wang YX, Poon CI, Poon KS, et al. Inhibitory actions of diphenyleneiodonium on endothelium-dependent vasodilatations in vitro and in vivo. Br J Pharmacol, 1993, 110(3): 1232-1238.
- 17-DMAG (Alvespimycin) HCl
Catalog No.:BCC1175
CAS No.:467214-21-7
- Alvespimycin
Catalog No.:BCC1346
CAS No.:467214-20-6
- Theaflavin
Catalog No.:BCN5419
CAS No.:4670-05-7
- Rehmannic acid
Catalog No.:BCN4632
CAS No.:467-81-2
- Coronaridine
Catalog No.:BCN3762
CAS No.:467-77-6
- Hecogenin
Catalog No.:BCN5408
CAS No.:467-55-0
- N-Methylcorydiniumiodide
Catalog No.:BCN7873
CAS No.:4668-64-6
- Z-Asp-OMe
Catalog No.:BCC2792
CAS No.:4668-42-2
- 3-O-(2'E ,4'E-decadienoyl)-20-O-acetylingenol
Catalog No.:BCN1437
CAS No.:466663-12-7
- 3-O-(2'E,4'E-Decadienoyl)ingenol
Catalog No.:BCN3768
CAS No.:466663-11-6
- Arteminin
Catalog No.:BCN3642
CAS No.:466639-11-2
- Cryptomeridiol
Catalog No.:BCN5516
CAS No.:4666-84-6
- Nootkatone
Catalog No.:BCN5517
CAS No.:4674-50-4
- Lu AE58054 Hydrochloride
Catalog No.:BCC1708
CAS No.:467458-02-2
- Lu AE58054
Catalog No.:BCC1707
CAS No.:467459-31-0
- Colupulone
Catalog No.:BCN8097
CAS No.:468-27-9
- Lupulon
Catalog No.:BCC8204
CAS No.:468-28-0
- Mesembrenone
Catalog No.:BCN3753
CAS No.:468-54-2
- Drimenol
Catalog No.:BCN7224
CAS No.:468-68-8
- Orphenadrine Citrate
Catalog No.:BCC4572
CAS No.:4682-36-4
- Norscopolamine
Catalog No.:BCN3983
CAS No.:4684-28-0
- Picrinine
Catalog No.:BCN5518
CAS No.:4684-32-6
- Dihydrocorynantheine
Catalog No.:BCN3747
CAS No.:4684-43-9
- 3-Benzofurancarboxaldehyde
Catalog No.:BCC8622
CAS No.:4687-25-6
Diphenyleneiodonium chloride, an inhibitor of reduced nicotinamide adenine dinucleotide phosphate oxidase, suppresses light-dependent induction of clock and DNA repair genes in zebrafish.[Pubmed:21804230]
Biol Pharm Bull. 2011;34(8):1343-7.
In most species, solar light is both a DNA-damaging agent and the key entraining stimulus for the endogenous circadian clock. The zebrafish is an attractive vertebrate system in which to study the influence of light on gene expression because the DNA repair proteins and circadian oscillators in this species are light-responsive. At the molecular level, light treatment of zebrafish cells induces the production of reactive oxygen species (ROS). ROS both alters the reduction-oxidation (redox) state of these cells and stimulates intracellular extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) cascades that transduce photic signals activating the transcription of particular light-responsive genes, including some clock genes and some DNA repair genes involved in photoreactivation. To date, however, the phototransducing molecules responsible for light-dependent ROS production have not been identified. Flavin-containing oxidases, such as reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, are versatile flavoenzymes that catalyze molecular oxidation in numerous metabolic pathways. Importantly, light induces the photoreduction of the flavin adenine dinucleotide (FAD) moiety in these oxidases, leading to ROS production. Here, we show in cultured zebrafish cells that Diphenyleneiodonium chloride (DPI), an inhibitor of NADPH oxidase, both suppresses ERK/MAPK activation and efficiently reduces light-dependent expression of clock and photoreactivation genes. Our results suggest that flavin-containing oxidases may be responsible for light-dependent ROS production and thus light-dependent gene expression in zebrafish. Our findings also support the existence of a regulatory link between photoreactivation and the circadian clock in this species.
Preferential inhibition of the plasma membrane NADH oxidase (NOX) activity by diphenyleneiodonium chloride with NADPH as donor.[Pubmed:11970854]
Antioxid Redox Signal. 2002 Feb;4(1):207-12.
The cell-surface NADH oxidase (NOX) protein of plant and animal cells will utilize both NADH and NADPH as reduced electron donors for activity. The two activities are distinguished by a differential inhibition by the redox inhibitor Diphenyleneiodonium chloride (DPI). Using both plasma membranes and cells, activity with NADPH as donor was markedly inhibited by DPI at submicromolar concentrations, whereas with NADH as donor, DPI was much less effective or had no effect on the activity. The possibility of the inhibition being the result of two different enzymes was eliminated by the use of a recombinant NOX protein. The findings support the concept that NOX proteins serve as terminal oxidases for plasma membrane electron transport involving cytosolic reduced pyridine nucleotides as the natural electron donors and with molecular oxygen as the electron acceptor.
The effects of diphenyleneiodonium and of 2,4-dichlorodiphenyleneiodonium on mitochondrial reactions. Mechanism of the inhibition of oxygen uptake as a consequence of the catalysis of the chloride/hydroxyl-ion exchange.[Pubmed:10893]
Biochem J. 1976 Aug 15;158(2):317-26.
1. Increasing the substrate concentration only decreased the inhibition of mitochondrial oxidations by diphenyleneiodonium or by 2,4-dichlorophenyleneiodonium by a small amount. 2. Diphenyleneiodonium and 2,4-dichlorodiphenyleneiodonium lowered the amounts of succinate, citrate and glutamate accumulated in the matrix of mitochondria in the presence of Cl-, but not in its absences. 2,4-Dichlorodiphenyleneiodonium decreased the accumulation of substrates by mitochondria oxidizing glycerol 3-phosphate. 3. Diphenyleneiodonium caused an alkalinization of the medium with an anaerobic suspension of mitochondria, which was only partly reversed by Triton X-100. 4. The rate of proton extrusion by mitochondria oxidizing succinate was not altered by diphenyleneiodonium or by 2,4-dichlorodiphenyleneiodium, although the rate of decay of proton pulses was increased. 5. 2,4-Dichlorodiphenyleneiodonium shifted the pH optimum for succinate oxidation by intact mitochondria from pH 7.2 to 8.0, whereas there was no effect on that of freeze-thawed mitochondria, which was pH 8.0. 6. The concentration of 2,4-dichlorophenyleneiodonium required to inhibit respiration by 50% is less the higher the absolute rate of oxygen uptake. 7. EDTA, but not EGTA [ethanedioxybis(ethylamine)-tetra-acetic acid] increased the inhibition of respiration by diphenyleneiodonium, 2,4-dichlorodiphenyleneiodonium and by tri-n-propyltin. 8. It is concluded that diphenyleneiodonium and 2,4-dichlorodiphenyleneiodonium limit respiration in Cl--containing medium by causing an acidification of the matrix, and that there are pH-sensitive sites in the respiratory chain between NADH and succinate, and between succinate and cytochrome c.
Different procedures of diphenyleneiodonium chloride addition affect neutrophil extracellular trap formation.[Pubmed:27179553]
Anal Biochem. 2016 Sep 15;509:60-66.
A unique strategy, in which invading microorganisms are being caught in web-like structures composed mainly of DNA, involves a recently described phenomenon called NETosis. This process seems to be related to the production of reactive oxygen species (ROS). In our study, the influence of Diphenyleneiodonium chloride (DPI), which diminishes ROS production, was assessed in the context of neutrophil extracellular trap (NET) release. According to protocol, two distinguished procedures were compared, the first one involving DPI elimination from sample before cell activation and the second one proceeding without the step of inhibitor washout. The kinetics of DNA release was monitored by fluorometric assay, and NET formation was observed by fluorescent microscopy. The addition of DPI to the sample led to a reduction of extracellular DNA release. The strongest inhibition was noticed after treatment with 10 muM DPI, which was removed from medium before stimulation with phorbol-12-myristate-13-acetate (PMA). Our findings confirmed that DPI is able to block NET creation. However, the addition of DPI together with PMA or the addition of inhibitor initially and then washing it out before stimulation resulted in different levels of NET formation. Finally, DPI that remained in the system induced specific morphological changes in the neutrophils' nuclei that was not observed in the DPI washed out from sample.
Identification of a novel small-molecule agonist for human G protein-coupled receptor 3.[Pubmed:24633425]
J Pharmacol Exp Ther. 2014 Jun;349(3):437-43.
G protein-coupled receptor 3 (GPR3) is an orphan G protein-coupled receptor (GPCR) predominantly expressed in mammalian brain and oocytes. GPR3 plays important roles in these two organs and is known as a Galphas-coupled receptor-activated constitutively in cells. However, the signal transduction pathway and pharmacological function of GPR3 remain unclear because of the lack of a specific ligand. By use of a human embryonic kidney 293 cell line stably expressing FLAG-GPR3-green fluorescent protein, a chemical screening for GPR3 ligands was performed using homogeneous time-resolved fluorescence cAMP assay. Diphenyleneiodonium chloride (DPI) was identified as a novel agonist of GPR3 with weak or no cross-reactivity with other GPCRs. DPI was further characterized to activate several GPR3-mediated signal transduction pathways, including Ca(2+) mobilization, cAMP accumulation, membrane recruitment of beta-arrestin2, and receptor desensitization. Parallel studies revealed that the activity of DPI is much more pronounced than sphingosine 1-phosphate, a previously reported GPR3 agonist. Our study identified a novel and specific agonist of GPR3, which provides a useful tool for further study of this orphan GPCR.
Inhibition of cytochrome P450 reductase by the diphenyliodonium cation. Kinetic analysis and covalent modifications.[Pubmed:8399148]
Biochemistry. 1993 Sep 28;32(38):10209-15.
Diphenyliodonium has been shown to be an irreversible, time-dependent inhibitor of NADPH cytochrome P450 oxidoreductase (EC 1.6.2.4) with the Ki for diphenyliodonium chloride being 2.8 mM. Kinetic studies have indicated that diphenyliodonium interacts with the reduced enzyme and NADPH is essential for inactivation to take place. Cytochrome c acts as a competitive substrate. The use of radiolabeled diphenyliodonium has enabled two sites of covalent modification to be identified. Isolation of radiolabeled cofactor followed by mass spectrometry has shown that a phenyl group is added to FMN while the FMN is effectively trapped in the reduced state. Trypsin digestion of S-carboxymethylated P450 reductase after inhibition with radiolabeled inhibitor shows covalent modification of the protein. Purification of a single radiolabelled peptide followed by automated Edman degradation has enabled identification of the second site of covalent attachment as Trp 419.
Inhibitory actions of diphenyleneiodonium on endothelium-dependent vasodilatations in vitro and in vivo.[Pubmed:7507779]
Br J Pharmacol. 1993 Nov;110(3):1232-8.
1. This study examined the in vitro and in vivo inhibitory effects of diphenyleneiodonium (DPI), a novel inhibitor of nitric oxide (NO) synthase, on endothelium-dependent vasodilatations. 2. DPI (3 x 10(-8)-3 x 10(-6) M) concentration-dependently inhibited acetylcholine (ACh)-induced relaxation in preconstricted rat thoracic aortic rings, with an IC50 of 1.8 x 10(-7) M and a maximal inhibition of nearly 100%. DPI (3 x 10(-6) M) also completely inhibited the relaxation induced by the calcium ionophore, A23187 but not by sodium nitroprusside (SNP). The inhibitory effect of DPI (3 x 10(-7) M) on ACh-induced relaxation was prevented by pretreatment with NADPH (5 x 10(-3) M) and FAD (5 x 10(-4) M) but not L-arginine (L-Arg, 2 x 10(-3) M). Pretreatment with NADPH did not alter the inhibitory effect of NG-nitro-L-arginine on ACh-induced relaxation. 3. The inhibitory effect of DPI on ACh-induced relaxation in the aortae lasted > 4 h after washout. In contrast to pretreatment, post-treatment (1 h later) with NADPH (5 x 10(-3) M) reversed only slightly the inhibitory effect of DPI. 4. In conscious rats, DPI (10(-5) mol kg-1) inhibited the depressor response to i.v. infused ACh, but not SNP. However, it caused only a transient pressor response which was previously shown to be due completely to sympathetic activation. 5. Thus, DPI is an efficacious and 'irreversible' inhibitor of endothelium-dependent vasodilatation in vivo and in vitro. The mechanism of the inhibition may involve antagonism of the effects of FAD and NADPH, co-factors of NO synthase. However, unlike the N0-substituted arginine analogues (another class of NO synthase inhibitors), DPI-induced suppression of endothelium-dependent vasodilatation in vivo does not lead to a sustained rise in blood pressure.
Inhibition of macrophage and endothelial cell nitric oxide synthase by diphenyleneiodonium and its analogs.[Pubmed:1703974]
FASEB J. 1991 Jan;5(1):98-103.
The cofactor requirements of macrophage nitric oxide (NO.) synthase suggest involvement of an NADPH-dependent flavoprotein. This prompted us to test the effect of the flavoprotein inhibitors diphenyleneiodonium (DPI), di-2-thienyliodonium (DTI), and iodoniumdiphenyl (ID) on the NO. synthases of macrophages and endothelium. DPI, DTI, and ID completely inhibited NO. synthesis by mouse macrophages, their lysates, and partially purified macrophage NO. synthase. Inhibition of NO. synthase by these agents was potent (IC50's 50-150 nM), irreversible, dependent on time and temperature, and independent of enzyme catalysis. The inhibition by DPI was blocked by NADPH, NADP+, or 2'5'-ADP, but not by NADH. Likewise, FAD or FMN, but not riboflavin or adenosine 5-diphosphoribose, protected NO. synthase from inhibition by DPI. Neither NADPH nor FAD reacted with DPI. Once NO. synthase was inhibited by DPI, neither NADPH nor FAD could restore its activity. DPI also inhibited acetylcholine-induced relaxation of norepinephrine-preconstricted rabbit aortic rings (IC50 300 nM). Inhibition of acetylcholine-induced relaxation persisted for at least 2 h after DPI was washed out. In contrast, DPI had no effect on norepinephrine-induced vasoconstriction itself nor on vasorelaxation induced by the NO.-generating agent sodium nitroprusside. These results suggest that NO. synthesis in both macrophages and endothelial cells depends on an NADPH-utilizing flavoprotein. As a new class of NO. synthase inhibitors, DPI and its analogs are likely to prove useful in analyzing the physiologic and pathophysiologic roles of NO(.).
Purification and some properties of the 45 kDa diphenylene iodonium-binding flavoprotein of neutrophil NADPH oxidase.[Pubmed:2154184]
Biochem J. 1990 Jan 1;265(1):95-100.
The 45 kDa diphenylene iodonium-binding flavoprotein of the human neutrophil superoxide-generating oxidase has been purified by affinity chromatography. The polypeptide was eluted from Blue Memsep or 2',5'-ADP-agarose columns with either NADP or low concentrations of the specific inhibitor diphenylene iodonium. The purified protein was shown to bind FAD at a ratio of 1.09 mol of FAD/mol of protein. The reconstituted flavoprotein had a fluorescence spectrum similar, but not identical, to that of free FAD. It had an isoelectric point of approx. 4.0. The reconstituted flavoprotein displayed no diaphorase activity towards a range of artificial electron acceptors. Polyclonal antibodies raised against the pure protein inhibited superoxide generation by solubilized oxidase in a dose-dependent manner, and inhibited superoxide generation when incubated with either cytosol or membrane fractions in a reconstituted system. These antibodies precipitated the 45 kDa polypeptide together with a haem-containing 23 kDa protein thought to be the small subunit of cytochrome b-245. Antibodies raised against cytochrome P-450 reductase also precipitated these two polypeptides. These results are consistent with the 45 kDa polypeptide being the flavoprotein of the neutrophil superoxide-generating oxidase.