353262-04-1

Basic information

• Product Name: NS-6180
• Synonyms: NS 6180;NS6180;NS-6180;4-[[3-(Trifluoromethyl)phenyl]methyl]-2H-1,4-benzothiazin-3(4H)-one
• CAS NO: 353262-04-1
• Molecular Formula: C16H12F3NOS
• Molecular Weight: 323.3327896
• Product Categories: Inhibitors
• Mol File: 353262-04-1.mol

Chemical Properties

• Boiling Point: 476.9±45.0 °C(Predicted)
• Appearance: white to beige/
• Density: 1.375±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble20mg/mL, clear
• PKA: 0.53±0.20(Predicted)
• CAS DataBase Reference: NS-6180(CAS DataBase Reference)
• NIST Chemistry Reference: NS-6180(353262-04-1)
• EPA Substance Registry System: NS-6180(353262-04-1)

Safety Data

• Hazard Codes: Xi,N
• Statements: 43-51/53
• Safety Statements: 61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 353262-04-1(Hazardous Substances Data)

Usage

Uses

Used in Immunomodulation:
NS-6180 is used as an immunomodulatory agent for enhancing the proliferation of A-NK and NA-NK cells, which are essential components of the immune system. This application helps in boosting the body's natural defense mechanisms against various diseases and infections.
Used in Inflammatory Bowel Disease Treatment:
NS-6180 is used as an anti-inflammatory agent in the treatment of inflammatory bowel disease. It acts as a KCa3.1 channel inhibitor, preventing T-cell activation and reducing inflammation in a rat model of the disease. This application has the potential to provide relief from the symptoms and improve the quality of life for patients suffering from inflammatory bowel disease.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, NS-6180 is used as a key component in the development of new drugs targeting immune-related disorders and inflammatory conditions. Its immunomodulatory and anti-inflammatory properties make it a valuable asset in the creation of innovative therapeutic solutions for various health issues.

Biological Activity

ns 6180 is a potent kca3.1 channel blocker. kca3.1 (the ca2+-activated k+ channel, encoded by the kcnn4 gene) plays a key role in these processes by participating in the regulation of calcium entry.

in vitro

ns6180 blocked cloned human kca3.1 channels via t250 and v275, while the same amino acid residues conferred sensitivity to triarylmethanes such as like tram-34. ns6180 blocked endogenously expressed kca3.1 channels in human, mouse and rat erythrocytes with similar potencies. rat and mouse splenocyte proliferation was suppressed ns6180 at submicrolar concentrations, which potently inhibited il-2 and ifn-g production, exerting smaller effects on il-4 and tnf-a and no effect on il-17 production. after induction of colitis, antibody staining exhibited kca3.1 channels in healthy colon and strong up-regulation in association with infiltrating immune cells [1].

in vivo

despite poor plasma exposure, ns6180 (3 and 10 mg·kg-1 b.i.d.) abolished colon inflammation and improved body weight gain effectively, just as the standard ibd drug sulfasalazine (300 mg·kg-1 q.d.). the benzothiazinone ns6180 was potent on recombinant and endogenously expressed kca3.1 channels, selectivity and molecular site of action. furthermore, the effect of ns6180 characterize its pharmacokinetics on the activity of t-lymphocytes from wild-type and kca3.1–/– knockout mice and show that it abolishes inflammation in an animal model of ibd [1].

IC 50

9, 14 and 15 nm for rat, human and mouse erythrocyte kca3.1 channels, respectively.

references

[1] strbk d, brown dt, jenkins dp, chen yj, coleman n, ando y, chiu p, jrgensen 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.