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Purity: ≥98%
| Targets |
The primary target of Ehp-inhibitor is EHP, a secreted protein from Staphylococcus aureus that inhibits the alternative complement activation pathway. Additionally, the compound targets Eph family tyrosine kinases. Eph receptors are involved in various cellular processes, including cell adhesion, migration, and angiogenesis. Inhibition of Eph receptors has been shown to increase glucose-stimulated insulin secretion from mouse and human pancreatic islets.
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| ln Vitro |
Ehp is a new secreted Staphylococcus aureus protein that potently inhibits the alternative complement activation pathway. Ehp was identified through a genomic scan as an uncharacterized secreted protein from S. aureus, and immunoblotting of conditioned S. aureus culture medium revealed that the Ehp protein was secreted at the highest levels during log-phase bacterial growth. The mature Ehp polypeptide is composed of 80 residues and is 44% identical to the complement inhibitory domain of S. aureus Efb (extracellular fibrinogen-binding protein). We observed preferential binding by Ehp to native and hydrolyzed C3 relative to fully active C3b and found that Ehp formed a subnanomolar affinity complex with these various forms of C3 by binding to its thioester-containing C3d domain. Site-directed mutagenesis demonstrated that Arg and Asn are important in forming the Ehp.C3d complex, but loss of these side chains did not completely disrupt Ehp/C3d binding. This suggested the presence of a second C3d-binding site in Ehp, which was mapped to the proximity of Ehp Asn. Further molecular level details of the Ehp/C3d interaction were revealed by solving the 2.7-A crystal structure of an Ehp.C3d complex in which the low affinity site had been mutationally inactivated. Ehp potently inhibited C3b deposition onto sensitized surfaces by the alternative complement activation pathway. This inhibition was directly related to Ehp/C3d binding and was more potent than that seen for Efb-C. An altered conformation in Ehp-bound C3 was detected by monoclonal antibody C3-9, which is specific for a neoantigen exposed in activated forms of C3. Our results suggest that increased inhibitory potency of Ehp relative to Efb-C is derived from the second C3-binding site in this new protein.
In vitro, Ehp-inhibitor is a novel and potent inhibitor of EHP. As an Eph family tyrosine kinase inhibitor, it targets Eph receptors. Specific IC50 values for inhibition of EHP or Eph receptors are not detailed in the available sources. The compound is soluble in DMSO at 100 mg/mL and is used in research related to bacterial pathogenesis and complement inhibition. |
| ln Vivo |
In vivo, inhibition of Eph receptors by Ehp-inhibitor results in an increase in glucose-stimulated insulin secretion from mouse and human pancreatic islets. This suggests potential applications in diabetes research. Specific animal model data are not detailed in the available sources. The compound is intended for research use only.
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| Enzyme Assay |
The EHP inhibition assay for Ehp-inhibitor involves incubating the compound with recombinant EHP protein and a complement component (such as C3b) in a buffer containing complement factors. The alternative complement pathway activity is measured by the deposition of C3b on a target surface or by the generation of complement activation products. Inhibition of EHP is assessed by the restoration of complement activity. For Eph receptor inhibition, a kinase assay using recombinant Eph receptor and a peptide substrate can be performed.
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| Cell Assay |
To evaluate the cellular activity of Ehp-inhibitor, cells expressing Eph receptors (such as pancreatic islet cells or cancer cell lines) are seeded in 96-well plates and treated with varying concentrations of the compound. Eph receptor phosphorylation is assessed by Western blot analysis using phospho-specific antibodies. Cell proliferation, migration, or adhesion assays can be performed to assess functional effects of Eph inhibition. Glucose-stimulated insulin secretion can be measured in pancreatic islet cells.
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| Animal Protocol |
The in vivo efficacy of Ehp-inhibitor can be evaluated in mouse models of diabetes or bacterial infection. For diabetes research, mice are administered Ehp-inhibitor and glucose tolerance tests are performed to assess insulin secretion. For bacterial infection models, mice are infected with Staphylococcus aureus and treated with the compound to assess its effect on complement activation and bacterial clearance. Specific protocols are not detailed in the available sources.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for Ehp-inhibitor are not provided in the available sources. The compound has a molecular weight of 303.32 and a molecular formula of C17H13N5O. It is soluble in DMSO at 100 mg/mL. It is typically stored at -20°C for long-term stability. Standard pharmacokinetic studies would typically involve administering the compound to rodents and measuring plasma concentrations over time using LC-MS/MS.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Ehp-inhibitor are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is an inhibitor of EHP and Eph receptors, and its toxicity profile would be expected to reflect its mechanism of action. Standard safety precautions should be followed when handling this compound.
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| References |
:J Biol Chem.2007 Oct 12;282(41):30051-61.
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| Additional Infomation |
Ehp-inhibitor is also known as Eph inhibitor 1. It is a novel and potent inhibitor of EHP, a secreted Staphylococcus aureus protein that inhibits the alternative complement activation pathway. It also targets Eph family tyrosine kinases, and inhibition of Eph receptors has been shown to increase glucose-stimulated insulin secretion. The compound has a molecular formula of C17H13N5O and a molecular weight of 303.32.
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| Molecular Formula |
C19H19N5O
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| Molecular Weight |
333.16
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| Exact Mass |
303.112
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| CAS # |
861249-77-6
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| Related CAS # |
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| PubChem CID |
11638044
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.756
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| LogP |
0.42
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
408
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)O)C2=C(N3C(=C(C=N3)C4=CN=CC=C4)N=C2)N
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| InChi Key |
RDCISORSAAOABP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H13N5O/c18-16-14(11-3-1-5-13(23)7-11)9-20-17-15(10-21-22(16)17)12-4-2-6-19-8-12/h1-10,23H,18H2
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| Chemical Name |
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| Synonyms |
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
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| 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) |
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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 | 3.0016 mL | 15.0078 mL | 30.0156 mL | |
| 5 mM | 0.6003 mL | 3.0016 mL | 6.0031 mL | |
| 10 mM | 0.3002 mL | 1.5008 mL | 3.0016 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.
 Ehp (SAV1155) is secreted at the highest levels during logphase growth.J Biol Chem.2007 Oct 12;282(41):30051-61. |
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 Ehp is a C3-binding protein related to Efb.J Biol Chem.2007 Oct 12;282(41):30051-61. |
 Characterization of Ehp binding to various C3 fragments by SPR.J Biol Chem.2007 Oct 12;282(41):30051-61. |
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