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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
IOX4 targets hypoxia-inducible factor prolyl-hydroxylase 2 (PHD2). PHD2 is a key enzyme that regulates the stability of hypoxia-inducible factor (HIF) by hydroxylating proline residues on HIF-α subunits, marking them for degradation. By inhibiting PHD2, IOX4 stabilizes HIF-α, leading to the accumulation of HIF and activation of HIF-dependent gene expression.
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| ln Vitro |
IOX4 (1-100 μM; 5 hours) found that the EC50 of HIF1α-induced MCF-7, Hep3B, and U2OS were, in that order, 114 μM, 86 μM, and 49.5 μM [1].
IOX4 is a potent inhibitor of PHD2 with an IC50 of 1.6 nM. It displays >1,000-fold selectivity for PHD2 over other 2OG-dependent dioxygenases, including JMJD isoforms, FBXL11, JARID1C, BBOX1, FIH, and FTO. It inhibits prolyl hydroxylation and increases HIF-1α levels in cells (IC50 ~5.6-11.7 µM). |
| ln Vivo |
IOX4 is active in vivo, inhibiting prolyl hydroxylation and increasing HIF-1α levels in cells. It induces HIF-1α and HIF-2α expression in mice. As shown by studies with mice, IOX4 is useful for in vivo work. It induces HIFα in wildtype mice with marked induction in the brain tissue.
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| Enzyme Assay |
The primary in vitro assay for IOX4 is a PHD2 enzyme activity assay, where the enzyme is incubated with a substrate and the compound, and the hydroxylation of the substrate is measured. The IC50 of 1.6 nM is determined from dose-response curves. Its selectivity over other dioxygenases is assessed in similar assays.
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| Cell Assay |
Cellular assays for IOX4 involve treating cells with the compound and measuring its effects on HIF-α levels and HIF-dependent gene expression. The stabilization of HIF-α is assessed by Western blot or ELISA. The activation of HIF target genes is measured by qPCR or reporter gene assays.
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| Animal Protocol |
In vivo animal experiments for IOX4 have been conducted in mice, where the compound is administered to assess its effects on HIF-α levels in various tissues. Its ability to induce HIF-α in the brain and other tissues has been demonstrated. These studies confirm its in vivo activity and utility for studying the HIF pathway.
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| ADME/Pharmacokinetics |
IOX4 has a molecular weight of 372.38 g/mol and a molecular formula of C16H20N6O4. It is a small molecule that is typically used as a research reagent. It is a potent and selective PHD2 inhibitor with an IC50 of 1.6 nM. It is active in vivo and induces HIF-α in mouse tissues.
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| Toxicity/Toxicokinetics |
The toxicological profile of IOX4 is not extensively detailed in the provided sources. As a research compound, it is not intended for human use. Standard safety precautions should be followed when handling. Its safety would need to be established through preclinical studies if it were to be developed for therapeutic applications.
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| References | |
| Additional Infomation |
IOX4 is a potent and selective inhibitor of PHD2 with an IC50 of 1.6 nM. It displays >1,000-fold selectivity for PHD2 over other dioxygenases. IOX4 induces HIF-α in cells and in mice, with marked induction in the brain. It is used as a research tool to study the HIF signaling pathway. It is available from various chemical suppliers for research purposes.
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| Molecular Formula |
C15H16N6O3
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|---|---|
| Molecular Weight |
328.32594203949
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| Exact Mass |
328.128
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| Elemental Analysis |
C, 54.87; H, 4.91; N, 25.60; O, 14.62
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| CAS # |
1154097-71-8
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| PubChem CID |
24812792
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
502.2±60.0 °C at 760 mmHg
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| Flash Point |
257.5±32.9 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.673
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| LogP |
0.73
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
544
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C(C1=CN=C(C=C1)N1C(C(=CN1)N1C=CN=N1)=O)=O)C(C)(C)C
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| InChi Key |
HWQQDVNGHZIALS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H16N6O3/c1-15(2,3)24-14(23)10-4-5-12(16-8-10)21-13(22)11(9-18-21)20-7-6-17-19-20/h4-9,18H,1-3H3
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| Chemical Name |
tert-butyl 6-[3-oxo-4-(triazol-1-yl)-1H-pyrazol-2-yl]pyridine-3-carboxylate
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| Synonyms |
IOX4; IOX-4; IOX 4.
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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 (~152.29 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.61 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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: ≥ 2.08 mg/mL (6.34 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 20.8 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: ≥ 2.08 mg/mL (6.34 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 | 3.0457 mL | 15.2286 mL | 30.4572 mL | |
| 5 mM | 0.6091 mL | 3.0457 mL | 6.0914 mL | |
| 10 mM | 0.3046 mL | 1.5229 mL | 3.0457 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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