NVP-231


Catalog No. size PriceQuantity
M7075-2 2mg solid $105
M7075-10 10mg solid $452

Description

Cas:362003-83-6

Product Information

NVP-231 is a potent, specific, and reversible CerK inhibitor that competitively inhibits binding of ceramide to CerK. NVP-231 is active in the low nanomolar range on purified as well as cellular CerK and abrogates phosphorylation of ceramide, resulting in decreased endogenous C1P levels. When combined with another ceramide metabolizing inhibitor, such as tamoxifen, NVP-231 synergistically increased ceramide levels and reduced cell growth. Therefore, NVP-231 represents a novel and promising compound for controlling ceramide metabolism that may provide insight into CerK physiological function.

 

Chemical Formula: C25H25N3O2S

 

Exact Mass: 431.16675

 

Molecular Weight: 431.55

 

Elemental Analysis: C, 69.58; H, 5.84; N, 9.74; O, 7.41; S, 7.43

 

Synonym: 

 

NVP231

NVP 231

NVP-231

 

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

 

 

Technical Data:

 

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

 

In Vitro

NVP-231 (0-500 nM; 24 hours) gradually reduces the cellular CerK activity, as measured by NBD-C1P formation, demonstrating that NVP-231 active in transfected cells. The IC50 for CerK in this cellular system is 59.70 ± 12 nM.

NVP-231 (0-1000 nM; 48 hours) decreases cell viability as a dose-dependent manner. This compound shows IC50 values of 1 μM in MCF-7 cells and 500 nM in NCI-H358 cells.

NVP-231 (1 μM; 24-72 hours) induces caspase-3 and caspase-9 cleavage in both cell lines. However, the highest caspase-3 and caspase-9 cleavage and activation occurred at 24 hours in MCF-7 cells, then decreases again. In NCI-H358 cells, caspase-3 and caspase-9 cleavage occurrs continuously over 72 hours.

NVP-231 (0-500 nM; 24 hours) causes a concentration-dependent up-regulation of cyclin B1 phosphorylation at Ser133 and a reduction of CDK1 phosphorylation at Tyr15. The total CDK1 expression also declined upon CerK inhibition

 

 

References

 

  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.

 

  1. 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.

 

  1. 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.

 

  1. 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.

 

  1. 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.RTRCRBT50415^^1/.65&2*1.05**5**2(*

 

Products are for research use only. Not for human use.

 

 

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