| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Targets sphingosine-1-phosphate lyase (S1PL), an intracellular pyridoxal-5‘-phosphate (PLP)-dependent enzyme that irreversibly cleaves S1P into phosphoethanolamine and hexadecenal, the final and committed step in S1P degradation. By inhibiting S1PL, A6770 prevents S1P breakdown and elevates cellular S1P levels.
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| ln Vitro |
Under normal conditions, A6770 generates concentration-dependent increases in [3H] dhS1P, with an EC50 range from 30 to 200 μM[1]. Rather than inhibiting SPP or activating SPHK, A6770 inhibits S1PL[2].
In IT-79MTC3 cells that endogenously express high levels of S1P lyase, A6770 induces accumulation of [3H]sphinganine-1-phosphate ([3H]dhS1P), the S1P lyase substrate, with an EC50 <0.01 microM. This effect is reduced in the presence of vitamin B6 (EC50 <100 microM), confirming that A6770 acts on the PLP-dependent S1PL enzyme. |
| ln Vivo |
Rats treated with A6770 (1, 10, 100 mg/kg; po; single dose) have fewer peripheral lymphocytes[2].
A6770 (1, 10, 100 mg/kg; p.o.; single dose) induces reductions in peripheral lymphocyte number in rats. By inhibiting S1P lyase, A6770 elevates tissue S1P levels, which in turn modulates S1P receptor signaling and lymphocyte trafficking. The reduction in peripheral lymphocyte count is a pharmacodynamic biomarker of S1PL inhibition. |
| Enzyme Assay |
S1PL enzyme activity assays are performed using recombinant human S1PL protein. The enzyme is incubated with [3H]dihydrosphingosine-1-phosphate (1 microM) as substrate in Tris-HCl buffer (pH 7.5) containing PLP (50 microM) and varying A6770 concentrations (0.001-100 microM) for 60 min at 37degC. The reaction is terminated by adding methanol. The product [3H]hexadecenal is extracted with organic solvent and quantified by liquid scintillation counting.
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| Cell Assay |
IT-79MTC3 cells are cultured in RPMI-1640 medium with 10% FBS. Cells are treated with A6770 (0.001-100 microM) for 4-24 h in the presence or absence of vitamin B6 (0-1000 microM). The accumulation of [3H]dhS1P is measured by extracting cellular lipids with chloroform/methanol (2:1, v/v). The organic phase is dried and resuspended in scintillation fluid for counting. EC50 values are calculated from dose-response curves.
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| Animal Protocol |
In rat PK/PD studies, male SD rats receive single oral doses of A6770 (1, 10, 100 mg/kg). Blood samples are collected at 0, 1, 2, 4, 8, and 24 h post-dose. Peripheral lymphocyte counts are determined by complete blood count (CBC) analysis. S1P levels in plasma and tissues are measured by LC-MS/MS. The relationship between drug exposure and lymphocyte reduction is analyzed.
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| ADME/Pharmacokinetics |
Detailed PK parameters for A6770 are not fully available. As an orally active small molecule (MW 140.1, C₆H₈N2O2), it is expected to have good oral bioavailability in rodents. The parent compound can be phosphorylated in vivo, and the phosphorylated metabolite is the active species that directly inhibits S1P lyase.
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| Toxicity/Toxicokinetics |
Toxicity data for A6770 is limited. THI (2-acetyl-4-tetrahydroxybutylimidazole), of which A6770 is a potential key metabolite, has known toxicities including lymphopenia and potential gastrointestinal effects. However, A6770 itself has not been extensively evaluated for toxicity. Standard acute and chronic toxicity studies would be required for development.
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| References | |
| Additional Infomation |
A6770 is a research chemical, not approved for clinical use. S1P lyase is a key enzyme in the S1P degradation pathway, and its inhibition offers a strategy to elevate S1P levels for therapeutic benefit in inflammatory and autoimmune diseases. A6770 is a useful tool for studying S1P lyase biology, S1P metabolism, and lymphocyte trafficking.
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| Molecular Formula |
C6H8N2O2
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|---|---|
| Molecular Weight |
140.14
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| Exact Mass |
140.058
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| CAS # |
1331754-16-5
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| PubChem CID |
53358898
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
384.1±34.0 °C at 760 mmHg
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| Flash Point |
186.1±25.7 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.577
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| LogP |
-1.64
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
10
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| Complexity |
138
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(=O)C1=NC=C(N1)CO
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| InChi Key |
JXDVIQLWMKAZBS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H8N2O2/c1-4(10)6-7-2-5(3-9)8-6/h2,9H,3H2,1H3,(H,7,8)
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| Chemical Name |
1-[5-(hydroxymethyl)-1H-imidazol-2-yl]ethanone
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 7.1357 mL | 35.6786 mL | 71.3572 mL | |
| 5 mM | 1.4271 mL | 7.1357 mL | 14.2714 mL | |
| 10 mM | 0.7136 mL | 3.5679 mL | 7.1357 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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