PTP1B-IN-3

PTP1B-IN-3 is a potent and orally active PTP1B inhibitor with IC₅₀s of 120 nM for both PTP1B and TCPTP. PTP1B-IN-3 has antidiabetic and anticancer effects^[1][2]. IC50 & Target: IC50: 120 nM (PTP1B), 120 nM (TCPTP) ^[2] In Vivo: 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].