WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555725
CAS#: 2561414-57-9 (HCl)
Description: GNF2133 is a potent and selective DYRK1A inhibitor (IC50 = 6 nM). In vitro, GNF2133 is able to proliferate both rodent and human β-cells. In vivo, GNF2133 demonstrated significant dose-dependent glucose disposal capacity and insulin secretion in response to glucose-potentiated arginine-induced insulin secretion (GPAIS) challenge in rat insulin promoter and diphtheria toxin A (RIP-DTA) mice.
MedKoo Cat#: 555725
Name: GNF2133 HCl
CAS#: 2561414-57-9 (HCl)
Chemical Formula: C24H31ClN6O2
Exact Mass: 434.243
Molecular Weight: 471.0
Elemental Analysis: C, 61.20; H, 6.63; Cl, 7.53; N, 17.84; O, 6.79
Related CAS #: 2561414-56-8 (free base) 2561414-57-9 (HCl)
Synonym: GNF2133 HCl; GNF2133 hydrochloride; GNF2133; GNF-2133; GNF 2133;
IUPAC/Chemical Name: 4-Ethyl-N-(4-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)pyridin-2-yl)piperazine-1-carboxamide hydrochloride
InChi Key: PKSHRWPMQDLRRB-UHFFFAOYSA-N
InChi Code: InChI=1S/C24H30N6O2.ClH/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);1H
SMILES Code: O=C(N1CCN(CC)CC1)NC2=NC=CC(C3=CN(C4CCOCC4)C5=C3C=CN=C5)=C2.[H]Cl
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >3 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | GNF2133 hydrochloride is a potent, selective and orally active DYRK1A inhibitor with IC50s of 0.0062, >50 µM for DYRK1A and GSK3β, respectively. |
| In vitro activity: | This report describes the discovery of a potent and selective DYRK1A inhibitor GNF2133, which was identified through optimization of a 6-azaindole screening hit. In vitro, GNF2133 is able to proliferate both rodent and human β-cells. Reference: J Med Chem. 2020 Mar 26;63(6):2958-2973. https://pubmed.ncbi.nlm.nih.gov/32077280/ |
| In vivo activity: | In vivo, GNF2133 demonstrated significant dose-dependent glucose disposal capacity and insulin secretion in response to glucose-potentiated arginine-induced insulin secretion (GPAIS) challenge in rat insulin promoter and diphtheria toxin A (RIP-DTA) mice. Reference: J Med Chem. 2020 Mar 26;63(6):2958-2973. https://pubmed.ncbi.nlm.nih.gov/32077280/ |
The following data is based on the product molecular weight 471.0 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Liu YA, Jin Q, Zou Y, Ding Q, Yan S, Wang Z, Hao X, Nguyen B, Zhang X, Pan J, Mo T, Jacobsen K, Lam T, Wu TY, Petrassi HM, Bursulaya B, DiDonato M, Gordon WP, Liu B, Baaten J, Hill R, Nguyen-Tran V, Qiu M, Zhang YQ, Kamireddy A, Espinola S, Deaton L, Ha S, Harb G, Jia Y, Li J, Shen W, Schumacher AM, Colman K, Glynne R, Pan S, McNamara P, Laffitte B, Meeusen S, Molteni V, Loren J. 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. doi: 10.1021/acs.jmedchem.9b01624. Epub 2020 Feb 20. PMID: 32077280. |
| In vitro protocol: | 1. Liu YA, Jin Q, Zou Y, Ding Q, Yan S, Wang Z, Hao X, Nguyen B, Zhang X, Pan J, Mo T, Jacobsen K, Lam T, Wu TY, Petrassi HM, Bursulaya B, DiDonato M, Gordon WP, Liu B, Baaten J, Hill R, Nguyen-Tran V, Qiu M, Zhang YQ, Kamireddy A, Espinola S, Deaton L, Ha S, Harb G, Jia Y, Li J, Shen W, Schumacher AM, Colman K, Glynne R, Pan S, McNamara P, Laffitte B, Meeusen S, Molteni V, Loren J. 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. doi: 10.1021/acs.jmedchem.9b01624. Epub 2020 Feb 20. PMID: 32077280. |
| In vivo protocol: | 1. Liu YA, Jin Q, Zou Y, Ding Q, Yan S, Wang Z, Hao X, Nguyen B, Zhang X, Pan J, Mo T, Jacobsen K, Lam T, Wu TY, Petrassi HM, Bursulaya B, DiDonato M, Gordon WP, Liu B, Baaten J, Hill R, Nguyen-Tran V, Qiu M, Zhang YQ, Kamireddy A, Espinola S, Deaton L, Ha S, Harb G, Jia Y, Li J, Shen W, Schumacher AM, Colman K, Glynne R, Pan S, McNamara P, Laffitte B, Meeusen S, Molteni V, Loren J. 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. doi: 10.1021/acs.jmedchem.9b01624. Epub 2020 Feb 20. PMID: 32077280. |
Liu YA, Jin Q, Zou Y, Ding Q, Yan S, Wang Z, Hao X, Nguyen B, Zhang X, Pan J, Mo T, Jacobsen K, Lam T, Wu TY, Petrassi HM, Bursulaya B, DiDonato M, Gordon WP, Liu B, Baaten J, Hill R, Nguyen-Tran V, Qiu M, Zhang YQ, Kamireddy A, Espinola S, Deaton L, Ha S, Harb G, Jia Y, Li J, Shen W, Schumacher AM, Colman K, Glynne R, Pan S, McNamara P, Laffitte B, Meeusen S, Molteni V, Loren J. 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. doi: 10.1021/acs.jmedchem.9b01624. Epub 2020 Feb 20. PMID: 32077280.
Autoimmune deficiency and destruction in either β-cell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting β-cell proliferation could be one approach toward diabetes intervention
