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GNF2133 hydrochloride is a potent, selective and orally active DYRK1A inhibitor with IC50s of 0.0062, >50 μM for DYRK1A and GSK3β, respectively. GNF2133 hydrochloride shows good proliferation potency and efficacy on rat and human primary β-cell. GNF2133 hydrochloride significantly improves glucose disposal capacity and increases insulin secretion. GNF2133 hydrochloride has the potential for the research of type 1 diabetes[1]. | [Biological Activity]
GNF2133 hydrochloride is a potent, selective and orally active DYRK1A inhibitor with IC50s of 0.0062, >50 μM for DYRK1A and GSK3β, respectively. GNF2133 hydrochloride shows good proliferation potency and efficacy on rat and human primary β-cell. GNF2133 hydrochloride significantly improves glucose disposal capacity and increases insulin secretion. GNF2133 hydrochloride has the potential for the research of type 1 diabetes[1].
GNF2133 hydrochloride (30 mg/kg; p.o.) shows good oral absorption with oral bioavailability of 22.3%[1].GNF2133 hydrochloride (30 mg/kg; p.o.; once a day for 5 days) shows the ability to proliferate β-cells in vivo[1].GNF2133 hydrochloride (3, 10, 30 mg/kg) significantly improves glucose disposal capacity and increased insulin secretion in RIP-DTA mice[1].Pharmacokinetic Parameters of GNF2133 hydrochloride in CD-1 mice[1]. plasma (iv) plasma (po) pancreas (po) CL (mL/min/kg)23.5Vss (L/kg)11AUC (h.nM)326810974144420 Cmax(nM)1977167513319tmax<(h)0.033.03.0Clast(nM)36.6191324t1/2<(h)6.63.46.6F (%)22.3CD-1 mice; 30 mg/kg; p.o.sup>[1]. | [in vivo]
GNF2133 hydrochloride (30 mg/kg; p.o.) shows good oral absorption with oral bioavailability of 22.3%[1].
GNF2133 hydrochloride (30 mg/kg; p.o.; once a day for 5 days) shows the ability to proliferate β-cells in vivo[1].
GNF2133 hydrochloride (3, 10, 30 mg/kg) significantly improves glucose disposal capacity and increased insulin secretion in RIP-DTA mice[1].
Pharmacokinetic Parameters of GNF2133 hydrochloride in CD-1 mice[1].
| plasma (iv) | plasma (po) | pancreas (po) | | CL (mL/min/kg) | 23.5 | / | / | | Vss (L/kg) | 11 | / | / | | AUC (h·nM) | 3268 | 10974 | 144420 | | Cmax(nM) | 1977 | 1675 | 13319 | | tmax<(h) | 0.03 | 3.0 | 3.0 | | Clast(nM) | 36.6 | 19 | 1324 | | t1/2<(h) | 6.6 | 3.4 | 6.6 | |
| F (%) | / | 22.3 | / | |
CD-1 mice; 30 mg/kg; p.o. [1].
| Animal Model: | CD-1 mice[1] | | Dosage: | 30 mg/kg | | Administration: | P.o. | | Result: | Showed good oral absorption and moderate plasma exposure with oral bioavailability of 22.3%. |
| Animal Model: | Wistar Han rat[1] | | Dosage: | 30 mg/kg (0.5% methylcellulose + Tween-80) | | Administration: | P.o.; once a day for 5 days | | Result: | Increased cyclin D1 levels and overall cell density, and increased in cell proliferation marker Ki67 and insulin. |
| Animal Model: | Diphtheria toxin A (RIP-DTA) mice[1] | | Dosage: | 3, 10, 30 mg/kg (20 mg/kg doxycycline (Dox) for 5 days) | | Administration: | P.o., once a day for 35 days | | Result: | Significantly improves glucose disposal capacity and increased insulin secretion. |
| [IC 50]
DYRK1A: 0.0062 μM (IC50); GSK3β: >50 μM (IC50) | [storage]
Store at -20°C | [References]
[1]. Liu YA, et al. Selective DYRK1A Inhibitor for the Treatment of Type 1 Diabetes: Discovery of 6-Azaindole Derivative GNF2133. J Med Chem. 2020 Mar 26;63(6):2958-2973. |
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