B-5354c
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| Category | Enzyme inhibitors |
| Catalog number | BBF-03221 |
| CAS | |
| Molecular Weight | 347.49 |
| Molecular Formula | C21H33NO3 |
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Description
B-5354c is a Sphingosine kinase (SPHK) inhibitor produced by SANK 71896. It has the activity of inhibiting SPHK with IC50 of 38 µmol/L.
Specification
| IUPAC Name | [(Z)-Tetradec-7-enyl] 4-amino-3-hydroxybenzoate |
| Canonical SMILES | CCCCCCC=CCCCCCCOC(=O)C1=CC(=C(C=C1)N)O |
| InChI | InChI=1S/C21H33NO3/c1-2-3-4-5-6-7-8-9-10-11-12-13-16-25-21(24)18-14-15-19(22)20(23)17-18/h7-8,14-15,17,23H,2-6,9-13,16,22H2,1H3/b8-7- |
| InChI Key | JXRQARJHAHNLMR-FPLPWBNLSA-N |
Properties
| Appearance | White Powder |
| Boiling Point | 511.4±45.0°C at 760 mmHg |
| Density | 1.0±0.1 g/cm3 |
Reference Reading
1. Chemosensitizing effects of sphingosine kinase-1 inhibition in prostate cancer cell and animal models
Dimitri Pchejetski, Nicolas Doumerc, Muriel Golzio, Maria Naymark, Justin Teissié, Takafumi Kohama, Jonathan Waxman, Bernard Malavaud, Olivier Cuvillier Mol Cancer Ther. 2008 Jul;7(7):1836-45. doi: 10.1158/1535-7163.MCT-07-2322.
We have previously reported that, in prostate cancer, inhibition of the oncogenic sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway is a key element in chemotherapy-induced apoptosis. Here, we show that selective pharmacologic inhibition of SphK1 triggers apoptosis in LNCaP and PC-3 prostate cancer cells, an effect that is reversed by SphK1 enforced expression. More importantly, we show for the first time that the up-regulation of the SphK1/S1P pathway plays a crucial role in the resistance of prostate cancer cells to chemotherapy. Importantly, pharmacologic SphK1 inhibition with the B-5354c compound sensitizes LNCaP and PC-3 cells to docetaxel and camptothecin, respectively. In vivo, camptothecin and B-5354c alone display a limited effect on tumor growth in PC-3 cells, whereas in combination there is a synergy of effect on tumor size with a significant increase in the ceramide to S1P sphingolipid ratio. To conclude, our study highlights the notion that drugs specifically designed to inhibit SphK1 could provide a means of enhancing the effects of conventional treatment through the prosurvival antiapoptotic SphK1/S1P pathway.
2. Activation of SphK1 by K6PC-5 Inhibits Oxygen-Glucose Deprivation/Reoxygenation-Induced Myocardial Cell Death
Jun-jie Shao, Yi Peng, Li-ming Wang, Jian-kai Wang, Xin Chen DNA Cell Biol. 2015 Nov;34(11):669-76. doi: 10.1089/dna.2015.2959. Epub 2015 Aug 26.
In the current study, we evaluated the potential effect of a novel sphingosine kinase 1 (SphK1) activator, K6PC-5, on oxygen-glucose deprivation (OGD)/reoxygenation-induced damages to myocardial cells. We demonstrated that K6PC-5 increased intracellular sphingosine-1-phosphate (S1P) content and remarkably inhibited OGD/reoxygenation-induced death of myocardial cells (H9c2/HL-1 lines and primary murine myocardiocytes). SphK1 inhibitors, B-5354c and SKI-II, or SphK1-siRNA knockdown not only aggregated OGD/reoxygenation-induced cytotoxicity but also nullified the cytoprotection by K6PC-5. On the other hand, overexpression of SphK1 alleviated H9c2 cell death by OGD/reoxygenation, and K6PC-5-mediated cytoprotection was also enhanced in SphK1 overexpressed cells. Molecularly, OGD/reoxygenation activated the mitochondrial death pathway, evidenced by reactive oxygen species (ROS) production, mitochondrial membrane potential reduction, and p53-cyclophilin D (Cyp-D) association, which were all alleviated by K6PC-5 or overexpression of SphK1, but exacerbated by SphK1 knockdown. Furthermore, OGD/reoxygenation induced prodeath ceramide production in myocardial cells, which was largely suppressed by K6PC-5. In the meantime, adding a cell-permeable short-chain ceramide (C6) mimicked OGD/reoxygenation actions and induced ROS production and the mitochondrial death pathway in myocardial cells. Together, we conclude that K6PC-5 inhibits OGD/reoxygenation-induced myocardial cell death probably through activating SphK1. The results of the study indicate a potential benefit of K6PC-5 on ischemic heart disease.
3. Clostridium perfringens alpha-toxin activates the sphingomyelin metabolism system in sheep erythrocytes
Sadayuki Ochi, Masataka Oda, Hisaaki Matsuda, Syusuke Ikari, Jun Sakurai J Biol Chem. 2004 Mar 26;279(13):12181-9. doi: 10.1074/jbc.M307046200. Epub 2003 Dec 30.
Clostridium perfringens alpha-toxin induces hemolysis of rabbit erythrocytes through the activation of glycerophospholipid metabolism. Sheep erythrocytes contain large amounts of sphingomyelin (SM) but not phosphatidylcholine. We investigated the relationship between the toxin-induced hemolysis and SM metabolic system in sheep erythrocytes. Alpha-toxin simultaneously induced hemolysis and a reduction in the levels of SM and formation of ceramide and sphingosine 1-phosphate (S1P). N-Oleoylethanolamine, a ceramidase inhibitor, inhibited the toxin-induced hemolysis and caused ceramide to accumulate in the toxin-treated cells. Furthermore, dl-threo-dihydrosphingosine and B-5354c, isolated from a novel marine bacterium, both sphingosine kinase inhibitors, blocked the toxin-induced hemolysis and production of S1P and caused sphingosine to accumulate. These observations suggest that the toxin-induced activation of the SM metabolic system is closely related to hemolysis. S1P potentiated the toxin-induced hemolysis of saponin-permeabilized erythrocytes but had no effect on that of intact cells. Preincubation of lysated sheep erythrocytes with pertussis toxin blocked the alpha-toxin-induced formation of ceramide from SM. In addition, incubation of C. botulinum C3 exoenzyme-treated lysates of sheep erythrocytes with alpha-toxin caused an accumulation of sphingosine and inhibition of the formation of S1P. These observations suggest that the alpha-toxin-induced hemolysis of sheep erythrocytes is dependent on the activation of the SM metabolic system through GTP-binding proteins, especially the formation of S1P.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
