GN44028 (GN-44028) is a novel and potent HIF-1α (hypoxia inducible factor) inhibitor with an IC50 of 14 nM. Inhibiting hypoxia-induced HIF-1α transcriptional activity without affecting HIF-1α mRNA expression, HIF-1α protein accumulation, or HIF-1α/HIF-1β heterodimerization.
Physicochemical Properties
| Molecular Formula | C18H15N3O2 |
| Molecular Weight | 305.330603837967 |
| Exact Mass | 305.116 |
| CAS # | 1421448-26-1 |
| Appearance | White to off-white solid powder |
| LogP | 3.5 |
| SMILES | N1=C(NC2=CC=C3OCCOC3=C2)C2CC3=C(C=2N1)C=CC=C3 |
| InChi Key | CGZKSZVSWAAUHE-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H15N3O2/c1-2-4-13-11(3-1)9-14-17(13)20-21-18(14)19-12-5-6-15-16(10-12)23-8-7-22-15/h1-6,10H,7-9H2,(H2,19,20,21) |
| Chemical Name | N-(2,3-dihydro-1,4-benzodioxin-6-yl)-1,4-dihydroindeno[1,2-c]pyrazol-3-amine |
| Synonyms | GN-44028 GN 44028 GN44028 |
| 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) |
Biological Activity
| ln Vitro | On HCT116, HepG2, and HeLa cells, GN44028 (Compound 2I, roughly 0–30 µM) exhibits anti-proliferative activity [1]. HeLa cells' hypoxia-induced VEGF mRNA expression is inhibited by GN44028 (0.001-1 μM, 4 h) [1]. In HCT116 cells, TGF-β-induced colony formation is eliminated by GN44028 (20 nM, 10 days) [2]. |
| ln Vivo | Mice with orthotopic tumors containing mixed PN12 and ME23 cells have longer survival times when given GN44028 (10 mg/kg, orally administered) [3]. In a subcutaneous colorectal cancer model, GN44028 (5 mg/kg, twice weekly, tail vein injection) suppresses tumor growth [2]. |
| Cell Assay |
RT-PCR[1] Cell Types: HeLa Cell Tested Concentrations: 0.001, 0.01, 0.1, 1μM Incubation Duration: 4 h Experimental Results: Inhibits hypoxia-induced HIF-1 transcriptional activity without affecting HIF-1α/HIF-1β heterodimer Polymerization. |
| Animal Protocol |
Animal/Disease Models: Mice with mixed orthotopic tumors of PN12 and ME23 cells [3] Doses: 10 mg/kg Route of Administration: po (oral gavage) Experimental Results: Both proneural and mesenchymal markers were diminished. Animal/Disease Models: subcutaneouscolorectal cancer model (HCT116) [2] Doses: 5 mg/kg Route of Administration: tail vein injection, twice a week Experimental Results: The lung nodules of tumor-bearing mice were diminished and the chemotherapy effect was enhanced. |
| References |
[1]. Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors. ACS Med Chem Lett. 2013 Jan 27;4(2):297-301. [2]. Tumor-associated macrophage-derived transforming growth factor-β promotes colorectal cancer progression through HIF1-TRIB3 signaling. Cancer Sci. 2021 Oct;112(10):4198-4207. [3]. Heterogeneity of subsets in glioblastoma mediated by Smad3 palmitoylation. Oncogenesis. 2021 Oct 27;10(10):72. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~163.76 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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: ≥ 2.5 mg/mL (8.19 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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: ≥ 2.5 mg/mL (8.19 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2751 mL | 16.3757 mL | 32.7514 mL | |
| 5 mM | 0.6550 mL | 3.2751 mL | 6.5503 mL | |
| 10 mM | 0.3275 mL | 1.6376 mL | 3.2751 mL |