For research use only. Not for therapeutic Use.
NS6180（Cat No.:I003287） is a potent and selective inhibitor of KCa3.1 ion channel with IC50 value of 9nM, which prevents T cell activation and inflammatory response.If you need, please feel free to contact us, we will reply to you within 24 hours.
| Catalog Number | I003287 |
| CAS Number | 353262-04-1 |
| Synonyms | 4-(3-(trifluoromethyl)benzyl)-2H-benzo[b][1,4]thiazin-3(4H)-one |
| Molecular Formula | C16H12F3NOS |
| Purity | ≥95% |
| Target | Potassium Channel |
| Solubility | DMSO: ≥ 47 mg/mL |
| Storage | 2-8°C |
| IC50 | 9 nM [1] |
| IUPAC Name | 4-[[3-(trifluoromethyl)phenyl]methyl]-1,4-benzothiazin-3-one |
| InChI | 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 |
| InChIKey | ZUIJXKLTUFCDGO-UHFFFAOYSA-N |
| SMILES | C1C(=O)N(C2=CC=CC=C2S1)CC3=CC(=CC=C3)C(F)(F)F |
| Reference | 1:Br J Pharmacol. 2013 Jan;168(2):432-44. doi: 10.1111/j.1476-5381.2012.02143.x. NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease.Strøbæk D,Brown DT,Jenkins DP,Chen YJ,Coleman N,Ando Y,Chiu P,Jørgensen S,Demnitz J,Wulff H,Christophersen P, PMID: 22891655 PMCID: PMC3572569 DOI: 10.1111/j.1476-5381.2012.02143.x </br><span>Abstract:</span> BACKGROUND AND PURPOSE: The K(Ca) 3.1 channel is a potential target for therapy of immune disease. We identified a compound from a new chemical class of K(Ca) 3.1 inhibitors and assessed in vitro and in vivo inhibition of immune responses.EXPERIMENTAL APPROACH: We characterized the benzothiazinone NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2H-1,4-benzothiazin-3(4H)-one) with respect to potency and molecular site of action on K(Ca) 3.1 channels, selectivity towards other targets, effects on T-cell activation as well as pharmacokinetics and inflammation control in colitis induced by 2,4-dinitrobenzene sulfonic acid, a rat model of inflammatory bowel disease (IBD).KEY RESULTS: NS6180 inhibited cloned human K(Ca) 3.1 channels (IC(50) = 9 nM) via T250 and V275, the same amino acid residues conferring sensitivity to triarylmethanes such as like TRAM-34. NS6180 inhibited endogenously expressed K(Ca) 3.1 channels in human, mouse and rat erythrocytes, with similar potencies (15-20 nM). NS6180 suppressed rat and mouse splenocyte proliferation at submicrolar concentrations and potently inhibited IL-2 and IFN-γ production, while exerting smaller effects on IL-4 and TNF-α and no effect on IL-17 production. Antibody staining showed K(Ca) 3.1 channels in healthy colon and strong up-regulation in association with infiltrating immune cells after induction of colitis. Despite poor plasma exposure, NS6180 (3 and 10 mg·kg(-1) b.i.d.) dampened colon inflammation and improved body weight gain as effectively as the standard IBD drug sulfasalazine (300 mg·kg(-1) q.d.).CONCLUSIONS AND IMPLICATIONS: NS6180 represents a novel class of K(Ca) 3.1 channel inhibitors which inhibited experimental colitis, suggesting K(Ca) 3.1 channels as targets for pharmacological control of intestinal inflammation.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
