PTP1B-IN-3 diammonium 

PTP1B-IN-3 diammonium is a potent and orally active PTP1B inhibitor with IC₅₀s of 120 nM for both PTP1B and TCPTP. PTP1B-IN-3 diammonium has antidiabetic and anticancer effects^[1][2].

IC50: 120 nM (PTP1B), 120 nM (TCPTP)^[2]

In diet-induced obese (DIO) mice, PTP1B-IN-3 (compounds 3g) exhibits dose dependent inhibition (60%, 80% and 100% inhibition at 1, 3 and 10 mg/kg, respectively) of glucose excursion when given orally 2 h before oral glucose challenge with an estimated ED₅₀ of 0.8 mg/kg^[1].
In the NDL2 Ptpn1 transgenic mice, PTP1B-IN-3 (compounds 3g; orally; 30 mg/kg for 21 days) shows a significant delay in the onset of tumor development in NDL2 Ptpn1^+/+ mice, extending the median tumor free days (T50) from 28 days to 75 days^[1].
In diet-induced obese (DIO) mice, PTP1B-IN-3 (compounds 3g) exhibits good oral bioavailability (F of 24%), slow clearance (CL of 0.71 mL/kg/min), and good elimination half live (t_1/2 of 6 h). The oral bioavailability in higher species such as rats (F of 4%) and squirrel monkeys (F of 2%) are substantially lower but excellent exposures are achieved with oral dosing^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

396.12

C₁₂H₁₃BrF₂N₃O₃P

2702673-78-5

固体

White to off-white

Room temperature in continental US; may vary elsewhere.

-20°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

• [1]. Yongxin Han, et al. Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro)methyl]phosphonic acid, a potent and orally active small molecule PTP1B inhibitor. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3200-5.  [Content Brief]

  [2]. Price N, et al. Safety and Efficacy of a Topical Sodium Channel Inhibitor (TV-45070) in Patients With Postherpetic Neuralgia (PHN): A Randomized, Controlled, Proof-of-Concept, Crossover Study, With a Subgroup Analysis of the Nav1.7 R1150W Genotype. Clin J Pain. 2017 Apr;33(4):310-318.  [Content Brief]