Physicochemical Properties
| Molecular Formula | C17H16N6O4 |
| CAS # | 2827693-99-0 |
| Appearance | Typically exists as solid at room temperature |
| 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 | HIF-1/2α-IN-1 (Compound #25) has an IC50 value of 0.92 μM and inhibits HIF-2α activity (0.01-100 μM) [1]. At higher concentrations, HIF-1α is inhibited by blocking the function of iron-sulfur cluster assembly, while HIF-1/2α-IN-1 (0-10 μM, 24 h) reduces HIF-2α by blocking IRE-dependent translation. Second Mediator (ISCA2) [1]. Iron starvation response is triggered by HIF-1/2α-IN-1 (1 μM, 24 hours) targeting ISCA2 [1]. The viability of 786-0 and RCC4 cells is decreased by HIF-1/2α-IN-1 (0-100 μM, 24 hours) (IC50=1.7 μM (786-0), 10.6 μM (786-0 VHL) and IC50=4.8 μM (RCC4), 71.0 μM (RCC4 VHL)) [1]. |
| ln Vivo | HIF-1/2α-IN-1 (Compound #25) (oral; 30, 60 mg/kg; daily) effectively inhibits ccRCC xenograft development in vivo [1]. |
| Cell Assay |
Cell Viability Assay [1] Cell Types: 786-0 cells and RCC4 cells Tested Concentrations: 0.01-100 μM Incubation Duration: 24 hrs (hours) Experimental Results: The cell viability of 786-0 cells and RCC4 cells was diminished. Western Blot Analysis[1] Cell Types: 786-0 cells and RCC10 cells Tested Concentrations: 0, 0.5, 1, 2.5, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished HIF-2α activity and protein levels. Higher concentrations or treatment durations reduce HIF-1α levels but do not promote proteasomal degradation of HIF-1/2α. Inhibits HIF-2α IRE (IRE-Luc)-driven luciferase production. IRP2 and TFRC increased in a dose-dependent manner, while FTH diminished. RT-PCR[1] Cell Types: 786-0 Cell Tested Concentrations: 0, 0.5, 1, 5 μM Incubation Duration: 24 hrs (hours) Experimental Results: Caused a dose-dependent decrease in the transcription of HIF-2α target genes VEGFA and POU5F1, but did not inhibit it HIF-2α transcription. |
| Animal Protocol |
Animal/Disease Models: NRG or balb/c (Bagg ALBino) mouse [1] (6-8 weeks old, male, 10 mice per group) Doses: 30, 60 mg/kg Doses: po (po (oral gavage)) daily Experimental Results: Dramatically inhibited tumor growth . It was well tolerated with no significant weight loss. |
| References |
[1]. ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma. Oncogene. 2022 Sep 12. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |