| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
BNS selectively targets prolyl hydroxylase 2 (PHD2), also known as EGLN1, a member of the 2-oxoglutarate-dependent dioxygenase family. PHD2 is the primary oxygen sensor that hydroxylates the proline residues (Pro-402 and Pro-564) of HIF-1α under normoxic conditions. This hydroxylation targets HIF-1α for ubiquitination by the von Hippel-Lindau (VHL) E3 ubiquitin ligase and subsequent proteasomal degradation. By inhibiting PHD2, BNS prevents the hydroxylation and degradation of HIF-1α, leading to its stabilization and accumulation. Stabilized HIF-1α translocates to the nucleus and activates the transcription of genes involved in angiogenesis, erythropoiesis, and metabolism.
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|---|---|
| ln Vitro |
In vitro, BNS has been shown to be a potent and selective inhibitor of PHD2. As a cell-penetrating compound, it can effectively enter cells and inhibit intracellular PHD2 activity. In MCF7 breast cancer cells, BNS modulates about 25% of hypoxia-regulated genes. This indicates that BNS can mimic a hypoxic response by stabilizing HIF-1α and activating its downstream target genes. The compound is used to study the role of HIF-1α in various cellular processes, including cell survival, proliferation, and metabolism under both normoxic and hypoxic conditions.
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| ln Vivo |
In vivo, BNS has been used to study the effects of PHD2 inhibition on angiogenesis and tissue protection. By stabilizing HIF-1α, BNS can promote the expression of angiogenic factors such as vascular endothelial growth factor (VEGF), which can stimulate the formation of new blood vessels. This makes PHD2 inhibitors like BNS potential therapeutic agents for conditions characterized by insufficient blood supply, such as ischemic heart disease and stroke. However, specific in vivo data for BNS are limited. The compound's cell permeability makes it suitable for in vivo studies.
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| Enzyme Assay |
Non-cellular in vitro assays for BNS involve measuring its inhibitory activity against purified recombinant human PHD2. A typical protocol uses a mass spectrometry-based assay or an enzyme-linked immunosorbent assay (ELISA) to measure the hydroxylation of a peptide substrate (e.g., a HIF-1α peptide) by PHD2. The enzyme is incubated with the peptide substrate, 2-oxoglutarate, Fe²⁺, and ascorbate in the presence of varying concentrations of BNS. The reaction is stopped, and the amount of hydroxylated peptide is measured. The IC50 value is determined from the concentration-response curve.
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| Cell Assay |
Cellular assays for BNS are performed using cell lines such as MCF7 or HeLa cells. Cells are treated with BNS at various concentrations for a period of time (e.g., 4-24 hours). To assess HIF-1α stabilization, cell lysates are prepared and analyzed by Western blotting using an antibody against HIF-1α. The expression of HIF-1α target genes, such as VEGF, GLUT1, and CA9, can be measured by RT-PCR. The effect of BNS on cell proliferation or survival can also be assessed using an MTT assay.
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| Animal Protocol |
In vivo animal studies for BNS are conducted in mouse models. A typical protocol involves administering BNS to mice via intraperitoneal (i.p.) or oral (p.o.) routes at doses such as 5-20 mg/kg. Treatment is typically given daily for 1-2 weeks. After the study, tissues are harvested for biochemical analysis. The levels of HIF-1α and its target genes are measured. Histological analysis is performed to assess angiogenesis or tissue protection. The compound's effects on physiological parameters such as hematocrit (due to increased erythropoietin) may also be monitored.
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| ADME/Pharmacokinetics |
BNS is a small molecule with a molecular weight of 420.46 and is soluble in DMSO at concentrations up to 20 mg/mL. For in vivo studies, it can be formulated in vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. Detailed pharmacokinetic parameters for BNS, such as half-life, bioavailability, and clearance, have not been fully reported in the available literature. However, its cell permeability and use in animal models suggest that it has sufficient bioavailability to exert its effects.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for BNS have not been extensively reported. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling BNS, including the use of personal protective equipment. The compound is typically stored as a powder at -20°C for up to three years or at 4°C for up to two years. No specific toxicity data, such as LD50 values, are available in the provided literature.
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| References | |
| Additional Infomation |
BNS is a valuable pharmacological tool for studying the role of PHD2 and HIF-1α in hypoxia signaling and angiogenesis. It is one of the few cell-penetrating PHD2 inhibitors available for research. The compound's ability to stabilize HIF-1α makes it useful for studying the cellular response to hypoxia and for validating PHD2 as a therapeutic target for ischemic diseases. BNS is not a clinically approved drug and has not entered clinical trials. Its primary application is in academic and pharmaceutical research.
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| Molecular Formula |
C18H16N2O6S2
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|---|---|
| Molecular Weight |
420.459442138672
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| Exact Mass |
420.044
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| CAS # |
1417440-37-9
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| PubChem CID |
71717922
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| Appearance |
White to off-white solid powder
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
786
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C=C(CC(O)=O)N(O)C1=NC(CS(CC1=CC=C2C(=C1)C=CC=C2)(=O)=O)=O
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| InChi Key |
QNCNQHCDQMPPGD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H16N2O6S2/c21-16(19-18-20(24)15(9-27-18)8-17(22)23)11-28(25,26)10-12-5-6-13-3-1-2-4-14(13)7-12/h1-7,9,24H,8,10-11H2,(H,22,23)
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| Chemical Name |
2-[3-hydroxy-2-[2-(naphthalen-2-ylmethylsulfonyl)acetyl]imino-1,3-thiazol-4-yl]acetic acid
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: ~100 mg/mL (~237.8 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (5.95 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3783 mL | 11.8917 mL | 23.7835 mL | |
| 5 mM | 0.4757 mL | 2.3783 mL | 4.7567 mL | |
| 10 mM | 0.2378 mL | 1.1892 mL | 2.3783 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02162680 | COMPLETEDWITH RESULTS | Drug: 1% lidocaine Drug: bacteriostatic normal saline (BNS) |
IV Insertion Pain | Duke University | 2010-03 | Phase 4 |
| NCT01303458 | COMPLETED | Behavioral: Basic Needs Surveillance (BNS) protocol | Low Income Families Basic Social Needs | Boston Medical Center | 2011-01 | Not Applicable |
| NCT03091283 | UNKNOWN STATUS | Educational Problems | Siriraj Hospital | 2017-04-01 | ||
| NCT04495868 | COMPLETEDWITH RESULTS | Drug: Bacteriostatic Normal Saline Drug: 1% Lidocaine |
Chronic Pain | Emory University | 2021-01-08 | Phase 4 |
| NCT01064830 | COMPLETEDWITH RESULTS | Drug: topical cyclosporine ophthalmic suspension 0.05% Drug: vehicle |
Brittle Nail Syndrome | University of North Carolina, Chapel Hill | 2010-02 | Phase 2 |
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