Synonym
NVP231; NVP 231; NVP-231
IUPAC/Chemical Name
N -[2-(Benzoylamino)-6-benzothiazolyl]tricyclo[3.3.1.13,7]decane-1-carboxamide
InChi Key
MVSSJPGNLQPWSW-UHFFFAOYSA-N
InChi Code
InChI=1S/C25H25N3O2S/c29-22(18-4-2-1-3-5-18)28-24-27-20-7-6-19(11-21(20)31-24)26-23(30)25-12-15-8-16(13-25)10-17(9-15)14-25/h1-7,11,15-17H,8-10,12-14H2,(H,26,30)(H,27,28,29)
SMILES Code
O=C(C1(C2)C[C@H]3C[C@@H]2C[C@H](C3)C1)NC4=CC=C5N=C(NC(C6=CC=CC=C6)=O)SC5=C4
Appearance
White to off-white 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, not in water
Shelf Life
>2 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
Biological target:
NVP 231 is a reversible ceramide kinase (CerK) inhibitor (IC50=12 nM) that competitively inhibits binding of ceramide to CerK.
In vitro activity:
To investigate whether CERK is involved in TNF-α-mediated immune responses, THP-1 monocytic cells were pre-treated with specific CERK inhibitor NVP-231(12 nM; Supplementary Fig. S1) before exposure to TNF-α. Treatment with NVP-231, followed by exposure to TNF-α, caused a significant reduction in the expression of phenotypic monocyte inflammatory markers including CD11c and HLA-DR at mRNA level and CD11c, CD11b and HLA-DR at protein level (Fig. 1A,B).
Reference: Sci Rep. 2021; 11: 8259. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050074/
In vivo activity:
NVP-231, a selective CERK inhibitor, was used to evaluate the involvement of CERK when cochlear outer mouse hair cells exposure to cisplatin or ceramide. At first, 5 μM cisplatin was mixed with to several concentrations of NVP-231. Outer hair cell death induced by 5 μM cisplatin was significantly exacerbated in the presence of NVP-231 at 3 μM or higher (Fig. 5; ANOVA followed by Bonferroni post hoc test; 3 μM NVP-231 group, n = 10, P = 0.008; 10 μM NVP-231 group, n = 10, P = 0.005). Later, in a different condition, 500 μM ceramide was combined with several concentrations of NVP-231. Outer hair cell death was severely damaged, starting with 10 μM NVP-231, and hair cells were completely unable to identify at 200 μM (Fig. 6; ANOVA followed by Bonferroni post hoc test; 10 μM NVP-231 group, n = 9, P = 0.000; 30 μM NVP-231 group, n = 10, P = 0.000; 100 μM NVP-231 group, n = 9, P = 0.000)
Reference: Toxicol Rep. 2016; 3: 450–457. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615927/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
10.0 |
23.20 |
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
431.55
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:
1. Al-Rashed F, Ahmad Z, Snider AJ, Thomas R, Kochumon S, Melhem M, Sindhu S, Obeid LM, Al-Mulla F, Hannun YA, Ahmad R. Ceramide kinase regulates TNF-α-induced immune responses in human monocytic cells. Sci Rep. 2021 Apr 15;11(1):8259. doi: 10.1038/s41598-021-87795-7. PMID: 33859296; PMCID: PMC8050074.
2. Schwalm S, Erhardt M, Römer I, Pfeilschifter J, Zangemeister-Wittke U, Huwiler A. Ceramide Kinase Is Upregulated in Metastatic Breast Cancer Cells and Contributes to Migration and Invasion by Activation of PI 3-Kinase and Akt. Int J Mol Sci. 2020 Feb 19;21(4):1396. doi: 10.3390/ijms21041396. PMID: 32092937; PMCID: PMC7073039.
3. Le Q, Tabuchi K, Hara A. Ceramide-1-phosphate protection of cochlear hair cells against cisplatin ototoxicity. Toxicol Rep. 2016 Apr 14;3:450-457. doi: 10.1016/j.toxrep.2016.04.003. PMID: 28959567; PMCID: PMC5615927.
4. Pastukhov O, Schwalm S, Römer I, Zangemeister-Wittke U, Pfeilschifter J, Huwiler A. Ceramide kinase contributes to proliferation but not to prostaglandin E2 formation in renal mesangial cells and fibroblasts. Cell Physiol Biochem. 2014;34(1):119-33. doi: 10.1159/000362989. Epub 2014 Jun 16. PMID: 24977486.
In vitro protocol:
1. Al-Rashed F, Ahmad Z, Snider AJ, Thomas R, Kochumon S, Melhem M, Sindhu S, Obeid LM, Al-Mulla F, Hannun YA, Ahmad R. Ceramide kinase regulates TNF-α-induced immune responses in human monocytic cells. Sci Rep. 2021 Apr 15;11(1):8259. doi: 10.1038/s41598-021-87795-7. PMID: 33859296; PMCID: PMC8050074.
2. Schwalm S, Erhardt M, Römer I, Pfeilschifter J, Zangemeister-Wittke U, Huwiler A. Ceramide Kinase Is Upregulated in Metastatic Breast Cancer Cells and Contributes to Migration and Invasion by Activation of PI 3-Kinase and Akt. Int J Mol Sci. 2020 Feb 19;21(4):1396. doi: 10.3390/ijms21041396. PMID: 32092937; PMCID: PMC7073039.
In vivo protocol:
1. Le Q, Tabuchi K, Hara A. Ceramide-1-phosphate protection of cochlear hair cells against cisplatin ototoxicity. Toxicol Rep. 2016 Apr 14;3:450-457. doi: 10.1016/j.toxrep.2016.04.003. PMID: 28959567; PMCID: PMC5615927.
2. Pastukhov O, Schwalm S, Römer I, Zangemeister-Wittke U, Pfeilschifter J, Huwiler A. Ceramide kinase contributes to proliferation but not to prostaglandin E2 formation in renal mesangial cells and fibroblasts. Cell Physiol Biochem. 2014;34(1):119-33. doi: 10.1159/000362989. Epub 2014 Jun 16. PMID: 24977486.
1: Pastukhov O, Schwalm S, Zangemeister-Wittke U, Fabbro D, Bornancin F, Japtok L, Kleuser B, Pfeilschifter J, Huwiler A. The ceramide kinase inhibitor NVP-231 inhibits breast and lung cancer cell proliferation by inducing M phase arrest and subsequent cell death. Br J Pharmacol. 2014 Dec;171(24):5829-44. doi: 10.1111/bph.12886. PubMed PMID: 25134723; PubMed Central PMCID: PMC4290720.
2: Pastukhov O, Schwalm S, Römer I, Zangemeister-Wittke U, Pfeilschifter J, Huwiler A. Ceramide kinase contributes to proliferation but not to prostaglandin E2 formation in renal mesangial cells and fibroblasts. Cell Physiol Biochem. 2014;34(1):119-33. doi: 10.1159/000362989. Epub 2014 Jun 16. PubMed PMID: 24977486.
3: Niwa S, Graf C, Bornancin F. Ceramide kinase deficiency impairs microendothelial cell angiogenesis in vitro. Microvasc Res. 2009 May;77(3):389-93. doi: 10.1016/j.mvr.2009.01.006. Epub 2009 Feb 6. PubMed PMID: 19323974.
4: Graf C, Rovina P, Bornancin F. A secondary assay for ceramide kinase inhibitors based on cell growth inhibition by short-chain ceramides. Anal Biochem. 2009 Jan 1;384(1):166-9. doi: 10.1016/j.ab.2008.09.008. Epub 2008 Sep 14. PubMed PMID: 18831956.
5: Graf C, Klumpp M, Habig M, Rovina P, Billich A, Baumruker T, Oberhauser B, Bornancin F. Targeting ceramide metabolism with a potent and specific ceramide kinase inhibitor. Mol Pharmacol. 2008 Oct;74(4):925-32. doi: 10.1124/mol.108.048652. Epub 2008 Jul 8. PubMed PMID: 18612076.
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