| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
DYRK1 DYRK1A 0.0062 μM (IC50) GSK3β >50 μM (IC50)
GNF2133 targets DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A). It is a potent and selective inhibitor of DYRK1A with an IC50 of 6.2 nM. It shows high selectivity over GSK3β with an IC50 of >50 µM. DYRK1A is a kinase involved in various cellular processes, including β-cell proliferation. By inhibiting DYRK1A, GNF2133 promotes β-cell proliferation and insulin secretion, making it a potential therapeutic agent for diabetes. |
|---|---|
| ln Vitro |
GNF2133 is a potent inhibitor of DYRK1A with an IC50 of 6.2 nM. It shows high selectivity over GSK3β with an IC50 of >50 µM. In vitro, GNF2133 significantly improved glucose disposal capacity and increased insulin secretion. It has good proliferative capacity and efficacy on rat and human primary beta cells. The compound's ability to promote β-cell proliferation and function is a key measure of its in vitro activity.
|
| ln Vivo |
GNF2133 (30 mg/kg; po) has a 22.3% oral bioavailability and excellent oral absorption.[1]. GNF2133 (30 mg/kg; po; once daily for five days) exhibits in vivo β-cell proliferation[1]. In RIP-DTA mice, GNF2133 (3, 10, 30 mg/kg) dramatically increases insulin secretion and glucose disposal capacity[1]. GNF2133's pharmacokinetic parameters in CD-1 mice[1]. plasma (iv) pancreas (po) and plasma (po) CL in milliliters per minute per kilogram 23.5 / / Vss (L/kg) AUC (h·nM) 3268 10974 144420 Clast(nM) 36.6 19 1324 t1/2<(h) Cmax(nM) 1977 1675 13319 tmax<(h) 0.03 3.0 3.0 30 mg/kg; po[1]; 6.6 3.4 6.6 F (%) / 22.3 / CD-1 mice.
GNF2133 demonstrates in vivo activity by improving glucose disposal and increasing insulin secretion. In RIP-DTA mice, GNF2133 (3, 10, 30 mg/kg) significantly improved glucose disposal capacity and increased insulin secretion. In CD-1 mice, GNF2133 (30 mg/kg; oral) showed moderate plasma exposure and good oral absorption with an oral bioavailability of 22.3%. In Wistar Han rats, GNF2133 (30 mg/kg; oral) increased the proliferation marker Ki67 and insulin levels. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for GNF2133 involves assessing its inhibition of DYRK1A kinase activity. Recombinant DYRK1A is incubated with the compound, ATP, and a substrate peptide. Kinase activity is measured by detecting the phosphorylation of the substrate. The IC50 value of 6.2 nM is determined from dose-response curves. Selectivity profiling against GSK3β is also performed, showing an IC50 of >50 µM.
|
| Cell Assay |
The in vitro cell-based assay for GNF2133 involves treating pancreatic β-cells with the compound and measuring its effects on cell proliferation and function. The compound's ability to increase insulin secretion and improve glucose disposal is assessed in cell-based models. The EC50 for its effects on β-cell proliferation may be determined. The compound's effects on β-cell proliferation and insulin secretion are key measures of its cellular activity.
|
| Animal Protocol |
Animal/Disease Models: CD-1 mice[1]
Doses: 30 mg/kg Route of Administration: Po Experimental Results: demonstrated good oral absorption and moderate plasma exposure with oral bioavailability of 22.3%. Animal/Disease Models: Wistar Han rat[1] Doses: 30 mg/kg (0.5% methylcellulose + Tween-80) Route of Administration: Po; one time/day for 5 days Experimental Results: Increased cyclin D1 levels and overall cell density, and increased in cell proliferation marker Ki67 and insulin. Animal/Disease Models: Diphtheria toxin A (RIP-DTA) mice[1] Doses: 3, 10, 30 mg/kg (20 mg/kg doxycycline (Dox) for 5 days) Route of Administration: Po, one time/day for 35 days Experimental Results: Dramatically improves glucose disposal capacity and increased insulin secretion. In vivo animal experiments for GNF2133 are conducted in models of type 1 diabetes. In RIP-DTA mice, animals are administered GNF2133 (3, 10, 30 mg/kg), and glucose disposal and insulin secretion are measured. In CD-1 mice, the compound's oral bioavailability is assessed. In Wistar Han rats, the effects on pancreatic β-cell proliferation are evaluated. The compound's ability to improve glucose tolerance and increase β-cell mass is assessed in these models. |
| ADME/Pharmacokinetics |
GNF2133 is an orally active compound. It has a molecular weight of 434.53 g/mol and a molecular formula of C24H30N6O2. It has an oral bioavailability of 22.3% in CD-1 mice. It is soluble in DMSO at 4.5 mg/mL. The compound is typically stored as a powder at -20°C.
|
| Toxicity/Toxicokinetics |
As a research compound, its safety profile is evaluated in standard cytotoxicity and acute toxicity assays. The compound is classified for research use only and is not intended for human therapeutic use. Comprehensive toxicological characterization would be required prior to any clinical development. The compound is typically handled with standard laboratory safety precautions.
|
| References | |
| Additional Infomation |
GNF2133 (CAS 2561414-56-8) is a potent, selective, and orally active DYRK1A inhibitor. It has an IC50 of 6.2 nM for DYRK1A. It has a molecular weight of 434.53 and a molecular formula of C24H30N6O2. It is being studied for type 1 diabetes. It is not approved for clinical use and is available only for research purposes.
|
| Molecular Formula |
C24H30N6O2
|
|---|---|
| Molecular Weight |
434.53
|
| Exact Mass |
434.243
|
| CAS # |
2561414-56-8
|
| Related CAS # |
GNF2133 hydrochloride;2561414-57-9
|
| PubChem CID |
145994392
|
| Appearance |
Off-white to pink solid powder
|
| LogP |
1.5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
32
|
| Complexity |
622
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N(C1N=CC=C(C2=CN(C3CCOCC3)C3=CN=CC=C23)C=1)C(N1CCN(CC)CC1)=O
|
| InChi Key |
SAZIAQSVBIWIDU-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H30N6O2/c1-2-28-9-11-29(12-10-28)24(31)27-23-15-18(3-8-26-23)21-17-30(19-5-13-32-14-6-19)22-16-25-7-4-20(21)22/h3-4,7-8,15-17,19H,2,5-6,9-14H2,1H3,(H,26,27,31)
|
| Chemical Name |
4-ethyl-N-[4-[1-(oxan-4-yl)pyrrolo[2,3-c]pyridin-3-yl]pyridin-2-yl]piperazine-1-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 4 mg/mL (9.21 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (1.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (5.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.5 mg/mL (1.15 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (5.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 0.5 mg/mL (1.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (5.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3013 mL | 11.5067 mL | 23.0134 mL | |
| 5 mM | 0.4603 mL | 2.3013 mL | 4.6027 mL | |
| 10 mM | 0.2301 mL | 1.1507 mL | 2.3013 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
