Tifenazoxide

Names

[ Name ]:
Tifenazoxide

Biological Activity

[Description]:

Tifenazoxide (NN414) is a potent, orally active and SUR1/Kir6.2 selective KATP channels opener. Tifenazoxide has antidiabetic effect, can inhibit glucose stimulated insulin release in vitro and in vivo, and has a beneficial effect on glucose homeostasis[1][2].

[Related Catalog]:

Research Areas >> Metabolic Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

[Target]

KATP channels[1][2]

[In Vitro]

Tifenazoxide (NN414) hyperpolarises βTC3 cell membranes, and inhibits insulin release from βTC6, from isolated rat islets and from human islets at least a 100-fold more potent than Diazoxide[2]. The EC50 values for Tifenazoxide and diazoxide are 0.45 and 31 µM, respectively in the patch-clamp assay. Tifenazoxide (100 µM) activates Kir6.2/SUR1 channels, but not Kir6.2/SUR2A or Kir6.2/SUR2 channels, expressed in Xenopus oocytes both in whole-cell and inside-out macropatch recordings[2]. Tifenazoxide is a potent inhibitor of glucose stimulated insulin release from βTC6 cells (IC50 = 0.15 µM)[1].

[In Vivo]

Tifenazoxide (NN414; 1.5 mg/kg; oral administration; twice daily; for 3 weeks; male VDF Zucker (fa/fa) rat) treatment for 3 weeks in VDF rats reduces basal hyperglycemia, improves glucose tolerance, and reduces hyperinsulinemia during an oral glucose tolerance test (OGTT) and improves insulin secretory responsiveness ex vivo[1]. Animal Model: Male Vancouver diabetic fatty (VDF) Zucker rat[1] Dosage: 1.5 mg/kg Administration: Oral administration; twice daily; for 3 weeks Result: Basal glucose was significantly reduced with the fall averaging 0.64 mM after 3 weeks of treatment.

[References]

[1]. Carr RD, et al. NN414, a SUR1/Kir6.2-selective potassium channel opener, reduces blood glucose and improves glucose tolerance in the VDF Zucker rat. Diabetes. 2003 Oct;52(10):2513-8.

[2]. Hansen JB. Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. Curr Med Chem. 2006;13(4):361-76.

Chemical & Physical Properties

[ Molecular Formula ]:
C₉H₁₀ClN₃O₂S₂

[ Molecular Weight ]:
291.77800

[ Exact Mass ]:
290.99000

[ PSA ]:
107.18000

[ LogP ]:
3.05910

[ Vapour Pressure ]:
3.22E-08mmHg at 25°C

MSDS

Click to get detail MSDS

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Articles

Mouse hypothalamic GT1-7 cells demonstrate AMPK-dependent intrinsic glucose-sensing behaviour.

Diabetologia 55 , 2432-44, (2012)

Hypothalamic glucose-excited (GE) neurons contribute to whole-body glucose homeostasis and participate in the detection of hypoglycaemia. This system appears defective in type 1 diabetes, in which hyp...

Related Compounds

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