PTP1B Inhibitor II, JTT-551

A cell-permeable dithiazolylmethylglycinate that acts as a PTP1B-selective tyrosine phosphatase inhibitor (K_i = 220 nM/PTP1B, 9.3 µM/TCPTP, >30 µM/CD45, >30 µM/LAR; Substrate = pNPP, Cat. nos. 6535-OP & 6537-OP) with a mixed-type mode of inhibition. Shown to enhance insulin-stimulated glucose uptake by rat L6 myotubes (by 17% and 36% in 10 min, respectively, at 10 and 30 µM; drug treatment starts 2 h prior to 10 nM insulin stimulation) in vitro and significantly enhance insulin-induced IR tyrosine phosphorylation (1 min) in liver of overnight fasted ob/ob mice (59% vs. 39% of C57BL/6J mice level, respectively, with or without single 10 mg/kg oral dosage 3 h prior to 3 U/kg insulin i.v. injection) in vivo. Daily oral administration is efficacious in reducing blood glucose and triglyceride levels among ob/ob (10 mg/kg/d) and db/db mice (30 mg/kg/d) without significant effect on body weight, while blood insulin level reduction is also seen among ob/ob, but not db/db mice.

A cell-permeable, orally available dithiazolylmethylglycinate that acts as a potent, selective, and reversible inhibitor of protein tyrosine phosphatase 1B (PTP1B; K_i = 220 nM). The inhibition appears to be of mixed type. Does not affect the activities of TCPTP, CD45, and LAR phosphatases (K_i = 9.3, >30 and >30 µM, respectively). Shown to increase insulin-stimulated glucose uptake in L6 rat skeletal muscle cells (~10-30 µM). Enhances insulin receptor phosphorylation in liver of ob/ob mice and reduces blood glucose level in a dose-dependent manner with hypoglycemic effects evident at >1 mg/kg (p.o.). Also effective in reducing blood glucose levels in db/db mice (>3 mg/kg, p.o.) without causing any weight gain.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Cell permeable: yes

Primary Target
PTP1B

Reversible: yes

Target K_i: 220 nM for PTP1B

Packaged under inert gas

Supplied as a diHCl salt.

Use only fresh DMSO for reconstitution.

Fukuda, S., et al. 2010. Diabetes Obes. Metab.12, 299.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)