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| 5mg |
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| Targets |
GN44028 targets hypoxia-inducible factor (HIF)-1α, specifically inhibiting its transcriptional activity. It does not affect HIF-1α mRNA expression, protein accumulation, or HIF-1α/HIF-1β heterodimerization in nuclei under hypoxic conditions. The compound has an IC₅₀ of 14 nM for HIF-1 inhibition.
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| 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].
In vitro, GN44028 demonstrates strong anti-proliferative activity against cancer cell lines including HCT116, HepG2, and HeLa at concentrations up to 30 µM. It inhibits hypoxia-induced HIF-1α transcriptional activity in a dose-dependent manner. The compound is a potent and selective HIF-1α inhibitor. |
| 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].
In vivo, GN44028 is orally active and has been studied for its anti-tumor activity. As a HIF-1α inhibitor, it has potential applications in cancer therapy by targeting the hypoxic tumor microenvironment. |
| Enzyme Assay |
HIF-1α transcriptional activity assays: Cancer cells (e.g., HCT116, HepG2, HeLa) are cultured under hypoxic conditions (1% O₂) in the presence of GN44028 at various concentrations (typically 1-100 nM). HIF-1α transcriptional activity is measured using a luciferase reporter gene assay with a hypoxia-responsive element (HRE)-driven luciferase construct. IC₅₀ values are calculated from dose-response curves.
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| 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. Cancer cell lines such as HCT116, HepG2, and HeLa are cultured in DMEM or RPMI-1640 with 10% FBS at 37°C with 5% CO₂. For hypoxia studies, cells are placed in a hypoxia chamber with 1% O₂. Cells are treated with GN44028 at various concentrations and cell viability is assessed by MTT or CellTiter-Glo assays. HIF-1α protein levels are measured by Western blot. HIF-1α mRNA expression is quantified by qRT-PCR. |
| 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. In vivo efficacy studies are conducted in tumor xenograft models. GN44028 is administered orally to tumor-bearing mice at specified doses. Tumor volume is measured over time. HIF-1α target gene expression is analyzed in tumor tissues. Pharmacokinetic parameters are assessed by measuring compound concentrations in plasma. |
| ADME/Pharmacokinetics |
GN44028 has molecular formula C₁₈H₁₅N₃O₂ and molecular weight 305.33. It is soluble in DMSO (30.53 mg/mL). Density is 1.421 g/cm³ (predicted). Purity is 99.52%. The compound is a potent and orally active HIF-1α inhibitor.
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| References |
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| Additional Infomation |
GN44028 is a novel and potent HIF-1α inhibitor with an IC₅₀ of 14 nM. It inhibits hypoxia-induced HIF-1α transcriptional activity through a unique mechanism that does not affect HIF-1α mRNA expression, protein accumulation, or HIF-1α/HIF-1β heterodimerization. The compound demonstrates strong anti-proliferative activity against various cancer cell lines and has potential applications in cancer therapy.
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| Molecular Formula |
C18H15N3O2
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|---|---|
| Molecular Weight |
305.330603837967
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| Exact Mass |
305.116
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| CAS # |
1421448-26-1
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| Appearance |
White to off-white solid powder
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| LogP |
3.5
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| SMILES |
N1=C(NC2=CC=C3OCCOC3=C2)C2CC3=C(C=2N1)C=CC=C3
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| InChi Key |
CGZKSZVSWAAUHE-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-1,4-dihydroindeno[1,2-c]pyrazol-3-amine
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| Synonyms |
GN-44028 GN 44028 GN44028
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~163.76 mM)
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| 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. View More
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. |
| 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 |
*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.
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