Synonym
NS6180; NS-6180; NS 6180.
IUPAC/Chemical Name
4-[[3-(Trifluoromethyl)phenyl]methyl]-2H-1,4-benzothiazin-3(4H)-one
InChi Key
ZUIJXKLTUFCDGO-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H12F3NOS/c17-16(18,19)12-5-3-4-11(8-12)9-20-13-6-1-2-7-14(13)22-10-15(20)21/h1-8H,9-10H2
SMILES Code
O=C1CSC2=CC=CC=C2N1CC3=CC=CC(C(F)(F)F)=C3
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:
NS6180 is a novel potent and selective KCa3.1 channel inhibitor (IC50 = 9 nM) that prevents T-cell activation and inflammation (IC50 = 9 nM).
In vitro activity:
NS6180 is a novel potent and selective KCa3.1 channel inhibitor (IC50 = 9 nM) that prevents T-cell activation and inflammation (IC50 = 9 nM).
In vivo activity:
In order to evaluate NS6180 efficacy in blocking KCa3.1 channels in a disease model, NS6180 was tested in DNBS-induced colitis in rats, a model of human IBD. In keeping with the known expression of KCa3.1 channels in intestinal epithelium (Rufo et al., 1997), immunohistochemical staining for these channels in colon sections from normal rats revealed KCa3.1 channels on the epithelial cells lining the well-aligned parallel crypts (Figure 7, upper panels) and on occasional ED1+ macrophages or CD43+ T cells in the muscularis mucosae and lamina propria (Figure 7, upper panels). In a separate series of experiments, groups of DNBS challenged rats were treated with two doses (3 and 10 mg·kg−1 b.i.d.) of NS6180 for 7 days in direct comparison with the IBD drug sulfasalazine (300 mg·kg−1 q.d.). The disease symptoms were followed, and Figure 8 shows the relative colon (Figure 8A) and body weight development (Figure 8B) of the different groups after 8 days of treatment. Both doses of NS6180 significantly improved weight gain and decreased inflammation induced swelling of the colon as determined by relative colon weight. The positive control sulfasalazine also significantly affected both body weight and colon inflammation (Figure 8). The effects of NS6180 and sulfasalazine did not differ significantly in magnitude.
Br J Pharmacol. 2013 Jan; 168(2): 432–444. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572569/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
20.0 |
61.90 |
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
323.33
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. Strøbæk D, Brown DT, Jenkins DP, Chen YJ, Coleman N, Ando Y, Chiu P, Jørgensen S, Demnitz J, Wulff H, Christophersen P. NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease. Br J Pharmacol. 2013 Jan;168(2):432-44. doi: 10.1111/j.1476-5381.2012.02143.x. PMID: 22891655; PMCID: PMC3572569.
2. 1. Strøbæk D, Brown DT, Jenkins DP, Chen YJ, Coleman N, Ando Y, Chiu P, Jørgensen S, Demnitz J, Wulff H, Christophersen P. NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease. Br J Pharmacol. 2013 Jan;168(2):432-44. doi: 10.1111/j.1476-5381.2012.02143.x. PMID: 22891655; PMCID: PMC3572569.
In vitro protocol:
1. Strøbæk D, Brown DT, Jenkins DP, Chen YJ, Coleman N, Ando Y, Chiu P, Jørgensen S, Demnitz J, Wulff H, Christophersen P. NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease. Br J Pharmacol. 2013 Jan;168(2):432-44. doi: 10.1111/j.1476-5381.2012.02143.x. PMID: 22891655; PMCID: PMC3572569.
In vivo protocol:
1. 1. Strøbæk D, Brown DT, Jenkins DP, Chen YJ, Coleman N, Ando Y, Chiu P, Jørgensen S, Demnitz J, Wulff H, Christophersen P. NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease. Br J Pharmacol. 2013 Jan;168(2):432-44. doi: 10.1111/j.1476-5381.2012.02143.x. PMID: 22891655; PMCID: PMC3572569.
1: Jenkins DP, Yu W, Brown BM, Løjkner LD, Wulff H. Development of a QPatch automated electrophysiology assay for identifying KCa3.1 inhibitors and activators. Assay Drug Dev Technol. 2013 Nov-Dec;11(9-10):551-60. doi: 10.1089/adt.2013.543. PubMed PMID: 24351043; PubMed Central PMCID: PMC3870577.
2: Koshy S, Wu D, Hu X, Tajhya RB, Huq R, Khan FS, Pennington MW, Wulff H, Yotnda P, Beeton C. Blocking KCa3.1 channels increases tumor cell killing by a subpopulation of human natural killer lymphocytes. PLoS One. 2013 Oct 11;8(10):e76740. doi: 10.1371/journal.pone.0076740. eCollection 2013. PubMed PMID: 24146918; PubMed Central PMCID: PMC3795664.
3: Jørgensen S, Dyhring T, Brown DT, Strøbæk D, Christophersen P, Demnitz J. A high-throughput screening campaign for detection of ca(2+)-activated k(+) channel activators and inhibitors using a fluorometric imaging plate reader-based tl(+)-influx assay. Assay Drug Dev Technol. 2013 Apr;11(3):163-72. doi: 10.1089/adt.2012.479. Epub 2012 Nov 30. PubMed PMID: 23198866.
4: Strøbæk D, Brown DT, Jenkins DP, Chen YJ, Coleman N, Ando Y, Chiu P, Jørgensen S, Demnitz J, Wulff H, Christophersen P. NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease. Br J Pharmacol. 2013 Jan;168(2):432-44. doi: 10.1111/j.1476-5381.2012.02143.x. PubMed PMID: 22891655; PubMed Central PMCID: PMC3572569.
