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| Targets |
HIF-2α-IN-3 targets hypoxia-inducible factor-2α (HIF-2α), a transcription factor that plays a critical role in cellular responses to hypoxia. HIF-2α forms heterodimers with ARNT (HIF-β) to activate the transcription of genes involved in angiogenesis, metabolism, and cell survival. By binding to an internal cavity of the HIF-2α PAS-B domain, HIF-2α-IN-3 inhibits HIF-2α-ARNT heterodimerization. This allosteric inhibition blocks HIF-2α transcriptional activity, thereby suppressing tumor growth and angiogenesis.
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| ln Vitro |
HIF-2α-IN-3 (compound 1) binds to the inner cavity of the HIF-2α PAS-B domain to prevent HIF-2α-ARNT (also called HIF-β) heterodimerization [1].
HIF-2α-IN-3 exhibits potent in vitro activity as a HIF-2α inhibitor. It has an IC50 of 0.4 μM and a Kd of 1.1 μM. The compound inhibits HIF-2α-ARNT heterodimerization by binding to an internal cavity of the HIF-2α PAS-B domain. It has anti-tumor activity in cancer cell lines. These in vitro activities confirm its potential as an anticancer agent targeting the HIF-2α pathway. |
| ln Vivo |
In vivo activity of HIF-2α-IN-3 has been evaluated in animal models of cancer and cardiovascular disease. As a HIF-2α inhibitor, the compound has anti-tumor activity. In vivo studies have demonstrated that HIF-2α-IN-3 inhibits tumor growth, likely through suppression of HIF-2α-mediated angiogenesis and metabolic reprogramming. It may also have applications in cardiovascular disease research. Further studies are needed to fully characterize its therapeutic potential.
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| Enzyme Assay |
In vitro binding assays for HIF-2α-IN-3 involve measuring its affinity for the HIF-2α PAS-B domain. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) are typically used to determine the dissociation constant (Kd) of 1.1 μM. In these assays, recombinant HIF-2α PAS-B domain is immobilized, and the compound is flowed over the surface to measure binding kinetics. Functional assays measuring HIF-2α-ARNT heterodimerization and transcriptional activity are used to confirm inhibition.
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| Cell Assay |
In vitro cellular assays for HIF-2α-IN-3 are conducted in cancer cell lines under hypoxic conditions. Cells are treated with the compound at various concentrations, and HIF-2α transcriptional activity is measured using luciferase reporter assays or by assessing the expression of HIF-2α target genes (e.g., VEGF, EPO) by qPCR. Cell proliferation and angiogenesis are assessed. These assays characterize the compound's anti-tumor activity.
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| Animal Protocol |
In vivo animal experiments with HIF-2α-IN-3 are conducted in mouse xenograft models of cancer. Immunodeficient mice are engrafted with cancer cells, and HIF-2α-IN-3 is administered orally or by intraperitoneal injection at varying doses. Tumor growth is measured over time, and tumor tissues are harvested for analysis of HIF-2α target gene expression, angiogenesis, and apoptosis. Pharmacodynamic studies are performed to confirm HIF-2α inhibition. These studies evaluate the compound's efficacy and mechanism of action in vivo.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for HIF-2α-IN-3 are limited. The compound has a molecular weight of 335.66 and is soluble in DMSO. Its bioavailability and half-life have not been extensively characterized. The compound is typically stored at -20°C. Further PK studies would be needed to support any potential clinical development.
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| Toxicity/Toxicokinetics |
HIF-2α-IN-3 is considered to have low toxicity based on its use as a research compound. However, comprehensive toxicological evaluations have not been extensively published. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
HIF-2α-IN-3 is an allosteric inhibitor of hypoxia-inducible factor-2α (HIF-2α). It has an IC50 of 0.4 μM and a Kd of 1.1 μM. The compound inhibits HIF-2α-ARNT heterodimerization by binding to an internal cavity of the HIF-2α PAS-B domain. It has anti-tumor activity and may be used in the study of cardiovascular disease. It is available in high purity (≥98%) for research applications. Its potent HIF-2α inhibition makes it a valuable tool for cancer and cardiovascular research.
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| Molecular Formula |
C12H6CLN5O5
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|---|---|
| Molecular Weight |
335.659540653229
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| Exact Mass |
335.005
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| CAS # |
313964-19-1
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| PubChem CID |
2836622
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
472
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1[N+](=O)[O-])NC1C=CC2C(C=1[N+](=O)[O-])=NON=2
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| InChi Key |
PQZKMXPISWCLCU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H6ClN5O5/c13-7-2-1-6(5-10(7)17(19)20)14-9-4-3-8-11(16-23-15-8)12(9)18(21)22/h1-5,14H
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| Chemical Name |
N-(4-chloro-3-nitrophenyl)-4-nitro-2,1,3-benzoxadiazol-5-amine
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| Synonyms |
HIF2αIN3; HIF 2α IN 3
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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 : ~12.5 mg/mL (~37.24 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9792 mL | 14.8960 mL | 29.7921 mL | |
| 5 mM | 0.5958 mL | 2.9792 mL | 5.9584 mL | |
| 10 mM | 0.2979 mL | 1.4896 mL | 2.9792 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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