| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
PHD-1-IN-1 targets PHD-1, a member of the prolyl hydroxylase domain (PHD) enzyme family. These enzymes are the cellular oxygen sensors that regulate the stability of hypoxia-inducible factors (HIFs). Under normoxic conditions, PHDs hydroxylate HIF-α subunits, targeting them for proteasomal degradation. By inhibiting PHD-1, PHD-1-IN-1 stabilizes HIF-1α, leading to the activation of the hypoxic response.
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| ln Vitro |
In vitro, PHD-1-IN-1 is a potent PHD-1 inhibitor with an IC50 of 0.034 μM. It shows moderate microsomal metabolic rate. It is used in studies of ischemia, anemia, cancer biology, and oxygen homeostasis. Its selectivity makes it valuable for distinguishing PHD1’s role from other PHD isoforms.
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| ln Vivo |
PHD-1-IN-1 (Compound 17; 0.5 mg/kg intravenously or 3 mg/kg orally) exhibits an AUC of 176 ng·h/mL, a B/P of 0.95, a Kp,uu of 1.11, and a Cmax of 0.8 μM [1].
In vivo, PHD-1-IN-1 is an orally active compound. By stabilizing HIF, it has potential applications in conditions where increasing the hypoxic response is beneficial, such as ischemia and anemia. Its in vivo efficacy would need to be confirmed in appropriate animal models. |
| Enzyme Assay |
Non-cellular assays for PHD-1-IN-1 involve measuring its inhibition of PHD-1 enzyme activity. These assays typically use recombinant PHD-1 and a peptide substrate (e.g., HIF-1α peptide) in the presence of cofactors (Fe2+, 2-oxoglutarate, ascorbate). The hydroxylation of the substrate is measured, and the IC50 is determined.
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| Cell Assay |
In vitro cellular assays for PHD-1-IN-1 are conducted to assess its effects on the HIF pathway. Cells are treated with the compound, and HIF-1α protein levels are measured by Western blot. The expression of HIF target genes (e.g., VEGF, EPO) is assessed by qPCR. Cellular assays for assessing its effects on cell viability and metabolism can also be performed.
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| Animal Protocol |
Animal/Disease Models: Male C57BL6 mice [1]
Doses: 3 mg/kg (oral) or 0.5 mg/kg (intravenous (iv) (iv)injection) (pharmacokinetic/PK/PK analysis) Route of Administration: oral or intravenous (iv) (iv)injection Experimental Results: Cmax is 0.8 μM, The AUC is 176 ng·h/mL, Kp,uu is 1.11, and B/P is 0.95. In vivo animal experiments with PHD-1-IN-1 are conducted in models of ischemia, anemia, and other conditions where HIF stabilization is beneficial. The compound is administered orally, and its effects on HIF target gene expression, tissue oxygen levels, and disease pathology are assessed. |
| ADME/Pharmacokinetics |
PHD-1-IN-1 is an orally active compound. It has a molecular weight of 314.3 g/mol. It is soluble in DMSO and is typically stored as a powder at -20°C. Its pharmacokinetic properties, such as bioavailability and half-life, would need to be characterized for in vivo use.
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| Toxicity/Toxicokinetics |
PHD-1-IN-1 is considered to be of low toxicity based on its use as a research compound. However, comprehensive toxicological data are not extensively published. The compound is intended for research use only and is not approved for human therapeutic use.
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| References | |
| Additional Infomation |
PHD-1-IN-1 is a potent, orally active inhibitor of HIF prolyl hydroxylase domain 1 (PHD-1) with an IC50 of 0.034 μM. It stabilizes HIF and is used in research on ischemia, anemia, cancer biology, and oxygen homeostasis. It has a unique binding mode with the Fe2+ ion.
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| Molecular Formula |
C13H8N4
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|---|---|
| Molecular Weight |
220.23
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| Exact Mass |
220.074
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| CAS # |
2009343-14-8
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| PubChem CID |
122540724
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| Appearance |
White to off-white solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
17
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| Complexity |
313
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(#N)C1=CC=C(C2N3N=CN=C3C=CC=2)C=C1
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| InChi Key |
DEYMFBHALUHGST-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H8N4/c14-8-10-4-6-11(7-5-10)12-2-1-3-13-15-9-16-17(12)13/h1-7,9H
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| Chemical Name |
4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile
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| Synonyms |
PHD1IN1; PHD 1 IN 1
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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 : ~195 mg/mL (~885.44 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 9.75 mg/mL (44.27 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 97.5 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: ≥ 9.75 mg/mL (44.27 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 97.5 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: ≥ 9.75 mg/mL (44.27 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 | 4.5407 mL | 22.7035 mL | 45.4071 mL | |
| 5 mM | 0.9081 mL | 4.5407 mL | 9.0814 mL | |
| 10 mM | 0.4541 mL | 2.2704 mL | 4.5407 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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