| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Ki: 0.16 µM (REV-ERBα)[1]
STL1267 is a high-affinity synthetic agonist of REV-ERB (specifically REV-ERBalpha), a nuclear receptor that functions as a transcription repressor of circadian and metabolic genes. It enhances the recruitment of the NCoR corepressor, which leads to repression of its target genes like BMAL1. |
|---|---|
| ln Vitro |
In HepG2 cells, STL1267 (5 µM; 24 h) enhances the gene expression of Mtnd1, Mtco1, Vicad, Lcad, Scad, Lkb1, Sirt1, Nampt, and Ppargc1a while decreasing the expression of BMAL1 [1].
STL1267 binds directly to the ligand-binding domain of REV-ERB with a Ki of 0.16 uM and an EC50 of 0.13 uM.Treatment with STL1267 (24h) shows no cytotoxicity and effectively decreases the gene expression of BMAL1 while increasing the expression of metabolic target genes like Mtnd1, Mtco1, Vicad, Lcad, and Scad. |
| ln Vivo |
In mice, STL1267 (50 mg/kg; ip; once) efficiently suppresses BMAL1 expression[1].
In vivo data are currently limited for this compound. As it can cross the blood-brain barrier, it is being explored for research into chronic diseases and inflammatory pain by modulating BMAL1 gene expression and circadian rhythms. |
| Enzyme Assay |
Cell-free binding assays are performed using a competition binding format. The REV-ERBalpha ligand-binding domain (LBD) is incubated with a radiolabeled known agonist and varying concentrations of STL1267. After reaching equilibrium, the bound and free ligands are separated via filtration, and the Ki is determined by scintillation counting.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: HepG2, C2C12 cells Tested Concentrations: 0-20 µM Incubation Duration: 24 h Experimental Results: demonstrated no adverse effects on cell viability up to the maximum dose examined 20 µM. RT-PCR[1] Cell Types: HepG2 cells Tested Concentrations: 5 µM Incubation Duration: 24 h Experimental Results: diminished the gene expression of BMAL1, increased the gene expression of Mtnd1, Mtco1, Vicad, Lcad, Scad, Lkb1, Sirt1, Nampt, Ppargc1a. Cell-based assays are performed in mammalian cell lines (e.g., U2OS). Cells are transfected with a luciferase reporter gene driven by a BMAL1 promoter or a REV-ERB response element. Following treatment with STL1267 for 24-48 hours, the luciferase activity is measured to quantify the half-maximal effective concentration (EC50) for repression of BMAL1 gene expression. |
| Animal Protocol |
Animal/Disease Models: 6-8 weeks, male C57Bl/6 J mice[1]
Doses: 50 mg/kg Route of Administration: Ip; once Experimental Results: demonstrated a plasma half-life of 1.6 h, effectively suppressed BMAL1 expression in the liver at 12 h post-administration. In vivo data is not available for this research compound. As a laboratory chemical for cell-based and in vitro studies, it is not typically formulated for animal pharmacokinetic or efficacy studies in a standard research setting. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties are not documented. As a laboratory chemical primarily for in vitro use, ADME (Absorption, Distribution, Metabolism, Excretion) data are not typically required or reported.
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| Toxicity/Toxicokinetics |
STL1267 has been evaluated for cytotoxicity and shows no cytotoxicity at effective concentrations in cell-based assays.This low cellular toxicity profile is important for its utility as a research tool for studying REV-ERB biology without confounding effects on cell viability.
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| References | |
| Additional Infomation |
STL1267 is a specific, high-affinity synthetic agonist of REV-ERB that provides a tool to investigate REV-ERB‘s role in regulating circadian rhythms and metabolism. Its unique ability to cross the blood-brain barrier distinguishes it from other REV-ERB agonists and allows for the study of the central nervous system's clock and its role in neurological and inflammatory pain. It is for research use only.
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| Molecular Formula |
C17H11CLN4O
|
|---|---|
| Molecular Weight |
322.748441934586
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| Exact Mass |
322.062
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| CAS # |
1429024-58-7
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| PubChem CID |
89479714
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| Appearance |
White to off-white solid powder
|
| LogP |
4.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
393
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC=C(C=C1)C2=CC=CC=C2OC3=NN4C(=NN=C4Cl)C=C3
|
| InChi Key |
XWHTYUYQMHCFMT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H11ClN4O/c18-17-20-19-15-10-11-16(21-22(15)17)23-14-9-5-4-8-13(14)12-6-2-1-3-7-12/h1-11H
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| Chemical Name |
3-chloro-6-(2-phenylphenoxy)-[1,2,4]triazolo[4,3-b]pyridazine
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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: 25 mg/mL (77.46 mM)
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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 | 3.0984 mL | 15.4919 mL | 30.9837 mL | |
| 5 mM | 0.6197 mL | 3.0984 mL | 6.1967 mL | |
| 10 mM | 0.3098 mL | 1.5492 mL | 3.0984 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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