Chelerythrine chlorideCAS# 3895-92-9 |
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 3895-92-9 | SDF | Download SDF |
PubChem ID | 72311 | Appearance | Orange powder |
Formula | C21H18ClNO4 | M.Wt | 383.82 |
Type of Compound | Nitrogen-containing Compounds | Storage | Desiccate at -20°C |
Synonyms | Toddaline chloride | ||
Solubility | DMSO : 4.35 mg/mL (11.33 mM; Need ultrasonic) | ||
Chemical Name | 1,2-dimethoxy-12-methyl-[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium;chloride | ||
SMILES | C[N+]1=C2C(=C3C=CC(=C(C3=C1)OC)OC)C=CC4=CC5=C(C=C42)OCO5.[Cl-] | ||
Standard InChIKey | WEEFNMFMNMASJY-UHFFFAOYSA-M | ||
Standard InChI | InChI=1S/C21H18NO4.ClH/c1-22-10-16-13(6-7-17(23-2)21(16)24-3)14-5-4-12-8-18-19(26-11-25-18)9-15(12)20(14)22;/h4-10H,11H2,1-3H3;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 | Cell-permeable inhibitor of protein kinase C (IC50 = 660 nM); competitive with respect to the phosphate acceptor and non-competitive with respect to ATP. Has a wide range of biological activities, including antiplatelet, anti-inflammatory, antibacterial and antitumor effects. Activates MAPK pathways, independent of PKC inhibition. Inhibits binding of BclXL to Bak (IC50 = 1.5 μM) or Bad proteins and stimulates apoptosis. |
Chelerythrine chloride Dilution Calculator
Chelerythrine chloride Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.6054 mL | 13.0269 mL | 26.0539 mL | 52.1078 mL | 65.1347 mL |
5 mM | 0.5211 mL | 2.6054 mL | 5.2108 mL | 10.4216 mL | 13.0269 mL |
10 mM | 0.2605 mL | 1.3027 mL | 2.6054 mL | 5.2108 mL | 6.5135 mL |
50 mM | 0.0521 mL | 0.2605 mL | 0.5211 mL | 1.0422 mL | 1.3027 mL |
100 mM | 0.0261 mL | 0.1303 mL | 0.2605 mL | 0.5211 mL | 0.6513 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
Chelerythrine Chloride is a potent, cell-permeable inhibitor of protein kinase C, with an IC50 of 660 nM, competitive with respect to the phosphate acceptor and non-competitive with respect to ATP.
In Vitro:Chelerythrine inhibits the BclXL-Bak BH3 peptide binding with IC50 of 1.5 μM and displaces Bax, a BH3-containing protein, from BclXL. Mammalian cells treated with Chelerythrine undergoes apoptosis with characteristic features that suggest involvement of the mitochondrial pathway[1]. Chelerythrine treatment inhibits LPS-induced TNF-α level and NO production in LPS-induced murine peritoneal macrophages through selective inhibition of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) activation. Moreover, the effects of chelerythrine on NO and cytokine TNF-α production can possibly be explained by the role of p38 MAPK and ERK1/2 in the regulation of inflammatory mediators expression[2]. Chelerythrine shows cytotoxic effect on the human monocytic leukaemia cells with LD50 value of 3.46 μM. Two hours after LPS stimulation, cells influenced by sanguinarine and Chelerythrine significantly decline the CCL-2 expression by a factors of 3.5 and 1.9[3]. Chelerythrine chloride significantly enhances the phosphorylation of ERK1/2 in a dose-dependent manner. In addition, chelerythrine chloride inhibits the phosphorylation of p38[4].
In Vivo:Chelerythrine displays significant anti-inflammatory effects in experimentally induced mice endotoxic shock model in vivo through inhibition of LPS-induced tumor necrosis factor-alpha (TNF-α) level and nitric oxide (NO) production in serum[2]. Chelerythrine chloride (5 mg/kg/day, i.p.) induces apoptosis of RCC cells without significant toxicity to mice. Chelerythrine Chloride treatment leads to a dose-dependent accumulation of p53[4].
References:
[1]. Chan, et al. Identification of chelerythrine as an inhibitor of BclXL function. J Biol Chem. 2003 Jun 6;278(23):20453-6.
[2]. Li W, et al. Effect of Chelerythrine Against Endotoxic Shock in Mice and Its Modulation of Inflammatory Mediators in Peritoneal Macrophages Through the Modulation of Mitogen-Activated Protein Kinase (MAPK) Pathway. Inflammation. 2012 Jul 24.
[3]. Pencikova K, et al. Investigation of sanguinarine and chelerythrine effects on LPS-induced inflammatory gene expression in THP-1 cell line. Phytomedicine. 2012 Jul 15;19(10):890-5. Epub 2012 May 14.
[4]. Chen XM, et al. Chelerythrine chloride induces apoptosis in renal cancer HEK-293 and SW-839 cell lines. Oncol Lett. 2016 Jun;11(6):3917-3924
[5]. Herbert JM, et al. Chelerythrine is a potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun. 1990 Nov 15;172(3):993-9.
- SBHA
Catalog No.:BCC2425
CAS No.:38937-66-5
- Isodeoxyelephantopin
Catalog No.:BCN4638
CAS No.:38927-54-7
- erythro-Guaiacylglycerol
Catalog No.:BCN5440
CAS No.:38916-91-5
- Halaminol C
Catalog No.:BCN1787
CAS No.:389125-68-2
- Halaminol B
Catalog No.:BCN1748
CAS No.:389125-59-1
- Halaminol A
Catalog No.:BCN1788
CAS No.:389125-56-8
- Z-Glu(OtBu)-OH
Catalog No.:BCC2776
CAS No.:3886-08-6
- CK 869
Catalog No.:BCC6347
CAS No.:388592-44-7
- PSN 375963 hydrochloride
Catalog No.:BCC7663
CAS No.:388575-52-8
- Tetrahydroepiberberine
Catalog No.:BCN2649
CAS No.:38853-67-7
- Emodin-1-O-glucoside
Catalog No.:BCN8512
CAS No.:38840-23-2
- Lapatinib Ditosylate
Catalog No.:BCC2083
CAS No.:388082-78-8
- Vitexin 4'-glucoside
Catalog No.:BCC9252
CAS No.:38950-94-6
- Isovitexin
Catalog No.:BCN5441
CAS No.:38953-85-4
- Icariside D2
Catalog No.:BCN7217
CAS No.:38954-02-8
- Piperlotine A
Catalog No.:BCN6481
CAS No.:389572-70-7
- Prasugrel hydrochloride
Catalog No.:BCC4291
CAS No.:389574-19-0
- Prasugrel Maleic acid
Catalog No.:BCC4292
CAS No.:389574-20-3
- Raspberry ketone glucoside
Catalog No.:BCC8244
CAS No.:38963-94-9
- N-Acetylnorloline
Catalog No.:BCN2005
CAS No.:38964-35-1
- Eriodictyol-7-O-glucoside
Catalog No.:BCN4743
CAS No.:38965-51-4
- 2'-O-Methylperlatolic acid
Catalog No.:BCN5442
CAS No.:38968-07-9
- Ophiopogonin B
Catalog No.:BCN5378
CAS No.:38971-41-4
- α-Tocopherol phosphate
Catalog No.:BCC5420
CAS No.:38976-17-9
Abeta1-42 increases the expression of neural KATP subunits Kir6.2/SUR1 via the NF-kappaB, p38 MAPK and PKC signal pathways in rat primary cholinergic neurons.[Pubmed:30868916]
Hum Exp Toxicol. 2019 Mar 14:960327119833742.
ATP-sensitive potassium channels (KATP) may mediate a potential neuroprotective role in Alzheimer's disease (AD). Given that exposure to Abeta1-42 in cultured primary cholinergic neurons for 72 h significantly upregulates the expression of KATP subunits Kir6.2/SUR1, we aim to study the underlying signal transduction mechanisms that are involved in Abeta1-42-induced upregulation of KATP subunits Kir6.2/SUR1. In the present study, we first identified the primary cultured rat cortical and hippocampal neurons using immunocytochemistry. 0.5 muM NF-kappaB inhibitor SN-50, 2 muM p38MAPK inhibitor SB203580 or 2 muM PKC inhibitor Chelerythrine chloride (CTC) were then added in three separate groups, followed by 2 muM Abeta1-42 30 min later in all 3 groups. Western Blot was performed 72 h later to detect the expression of KATP subunits Kir6.2/SUR1. We found that Abeta1-42 significantly increased the level of KATP subunits Kir6.2/SUR1 expression at 72 h when compared with the control group ( p < 0.05). However, when compared with the Abeta1-42 group, the level of KATP subunits Kir6.2/SUR1 expression at 72 h significantly decreased in the SN50 + Abeta1-42 group, SB203580 + Abeta1-42 group, and the CTC + Abeta1-42 group ( p < 0.05). Our findings suggest that the NF-kappaB, p38 MAPK, and PKC signal pathways are partially involved in the upregulation of KATP subunits Kir6.2/SUR1 expression induced by Abeta1-42 cytotoxicity in neurons, which supports a potential theoretical basis of targeting these signal pathways in the treatment of AD.
Identification of chelerythrine as an inhibitor of BclXL function.[Pubmed:12702731]
J Biol Chem. 2003 Jun 6;278(23):20453-6.
The identification of small molecule inhibitors of antiapoptotic Bcl-2 family members has opened up new therapeutic opportunities, while the vast diversity of chemical structures and biological activities of natural products are yet to be systematically exploited. Here we report the identification of chelerythrine as an inhibitor of BclXL-Bak Bcl-2 homology 3 (BH3) domain binding through a high throughput screening of 107,423 extracts derived from natural products. Chelerythrine inhibited the BclXL-Bak BH3 peptide binding with IC50 of 1.5 micro m and displaced Bax, a BH3-containing protein, from BclXL. Mammalian cells treated with chelerythrine underwent apoptosis with characteristic features that suggest involvement of the mitochondrial pathway. While staurosporine, H7, etoposide, and chelerythrine released cytochrome c from mitochondria in intact cells, only chelerythrine released cytochrome c from isolated mitochondria. Furthermore BclXL-overexpressing cells that were completely resistant to apoptotic stimuli used in this study remained sensitive to chelerythrine. Although chelerythrine is widely known as a protein kinase C inhibitor, the mechanism by which it mediates apoptosis remain controversial. Our data suggest that chelerythrine triggers apoptosis through a mechanism that involves direct targeting of Bcl-2 family proteins.
Activation of p38 and c-Jun N-terminal kinase pathways and induction of apoptosis by chelerythrine do not require inhibition of protein kinase C.[Pubmed:10734112]
J Biol Chem. 2000 Mar 31;275(13):9612-9.
Chelerythrine, a natural benzophenanthridine alkaloid, has been reported to mediate a variety of biological activities, including inhibition of protein kinase C (PKC). Here we report that chelerythrine induced time- and dose-dependent activation of JNK1 and p38 in HeLa cells, which was mediated the upstream kinases, MEKK1 and MKK4. However, treatment with two other potent and selective PKC inhibitors, GF-109203X and Go6983, or down-regulation of PKC activity by prolonged treatment with phorbol 12-myristate 13-acetate had no effect on JNK1 and p38 activities. Furthermore, under the conditions where JNK1 and p38 were activated, we did not observe any significant inhibitory effect of chelerythrine on the activities of PKC isozymes present in HeLa cells. Interestingly, pretreatment with the antioxidants, N-acetyl-L-cysteine, dithiothreitol, and glutathione, impaired chelerythrine-induced JNK1 and p38 activation. In addition, chelerythrine induced apoptosis that was blocked by the antioxidants and the dominant-negative mutants of MEKK1, MKK4, JNK1, and p38. Together, these results uncover a novel biochemical property of chelerythrine, i.e. activation of MEKK1- and MKK4-dependent JNK1 and p38 pathways through an oxidative stress mechanism, which mediate the induction of apoptosis, but are independent of PKC inhibition.
Angoline and chelerythrine, benzophenanthridine alkaloids that do not inhibit protein kinase C.[Pubmed:9677417]
J Biol Chem. 1998 Jul 31;273(31):19829-33.
Starting with an extract derived from the stem of Macleaya cordata (Papaveraceae) that was active in the process of inhibiting phorbol 12,13-dibutyrate binding to partially purified protein kinase C (PKC), the benzophenanthridine alkaloid angoline was isolated and identified. This discovery appeared in context, as a related benzophenanthridine alkaloid, chelerythrine, has been reported to mediate a variety of biological activities, including potent and selective inhibition of protein kinase C (PKC). However, in our studies, angoline was not observed to function as a potent inhibitor of PKC. Moreover, we were unable to confirm the reported inhibitory activity of chelerythrine. In a comprehensive series of studies performed with various PKC isozymes derived from a variety of mammalian species, neither chelerythrine nor angoline inhibited activity with high potency. To the contrary, chelerythrine stimulated PKC activity in the cytosolic fractions of rat and mouse brain in concentrations up to 100 microM. In addition, chelerythrine and angoline did not inhibit [3H]phorbol 12,13-dibutyrate binding to the regulatory domain of PKC at concentrations up to 40 microg/ml, and no significant alteration of PKC-alpha, -beta, or -gamma translocation was observed with human leukemia (HL-60) cells in culture. Further, chelerythrine did not inhibit 12-O-tetradecanoylphorbol 13-acetate-induced ornithine decarboxylase activity with cultured mouse 308 cells, but angoline was active in this capacity with an IC50 value of 1.0 microg/ml. A relatively large number of biological responses have been reported in studies conducted with chelerythrine, and alteration of PKC activity has been considered as a potential mechanism of action. In light of the current report, mechanisms independent of PKC inhibition should be considered as responsible for these effects.
Chelerythrine is a potent and specific inhibitor of protein kinase C.[Pubmed:2244923]
Biochem Biophys Res Commun. 1990 Nov 15;172(3):993-9.
The benzophenanthridine alkaloid chelerythrine is a potent, selective antagonist of the Ca++/phospholopid-dependent protein kinase (Protein kinase C: PKC) from the rat brain. Half-maximal inhibition of the kinase occurs at 0.66 microM. Chelerythrine interacted with the catalytic domain of PKC, was a competitive inhibitor with respect to the phosphate acceptor (histone IIIS) (Ki = 0.7 microM) and a non-competitive inhibitor with respect to ATP. This effect was further evidenced by the fact that chelerythrine inhibited native PKC and its catalytic fragment identically and did not affect [3H]- phorbol 12,13 dibutyrate binding to PKC. Chelerythrine selectively inhibited PKC compared to tyrosine protein kinase, cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase. The potent antitumoral activity of celerythrine measured in vitro might be due at least in part to inhibition of PKC and thus suggests that PKC may be a model for rational design of antitumor drugs.