| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
SR12418 targets the nuclear receptors REV-ERBalpha (NR1D1) and REV-ERBbeta (NR1D2). As a synthetic ligand, it likely acts as a REV-ERB agonist, regulating the expression of target genes involved in the circadian rhythm, lipid and glucose metabolism, and inflammatory responses. Modulation of REV-ERB activity has been shown to regulate TH17 cell differentiation and IL-17A production.
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| ln Vitro |
TH17 cell proliferation is inhibited by SR12418 (5 μM; 96 hours) [1]. In TH17 polarizing circumstances, SR12418 (5 and 10 μM; 4 d) suppresses cell differentiation [1].
In a TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) biochemical assay, SR12418 binds to REV-ERBalpha with an IC50 of 68 nM and to REV-ERBbeta with an IC50 of 119 nM. In cellular assays using EL4 cells (mouse lymphoma line), SR12418 (5 uM) inhibits IL-17A expression and suppresses TH17 cell differentiation, demonstrating its ability to modulate this key inflammatory pathway. |
| ln Vivo |
SR12418 (ip; 50 mg/kg; twice daily) inhibits the development and severity of experimental autoimmune encephalomyelitis [1]. SR12418 (ip; 50 mg/kg; twice daily; starting on day 18 post-immunization) has shown efficacy in an intervention study in relapsing-remitting experimental autoimmune encephalomyelitis [1].
In a mouse model of relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE, a model for multiple sclerosis), SR12418 is efficacious. It inhibits the development and severity of disease when administered intraperitoneally at a dose of 50 mg/kg twice daily. When treatment is started on day 18 post-immunization (an intervention study), it still shows efficacy, reducing disease severity in an established model. It is also used in colitis research. |
| Enzyme Assay |
The binding affinity is determined using a TR-FRET competitive binding assay. A recombinant LanthaScreen™ REV-ERBalpha ligand binding domain (LBD) tagged with GST is mixed with a terbium-labeled anti-GST antibody, a fluorescent REV-ERBalpha tracer, and varying concentrations of SR12418. After incubation, the TR-FRET ratio (520 nm/490 nm) is measured. The binding of SR12418 competes with the tracer, leading to a loss of FRET signal and allowing for the calculation of the IC50.
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| Cell Assay |
RT-PCR[1]
Cell Types: TH17 Cell Tested Concentrations: 5 μM Incubation Duration: 96 hrs (hours) Experimental Results: Inhibition of TH17-mediated gene expression and Nfil3. Cell Differentiation Assay[1] Cell Types: Mouse CD4+ T cells Tested Concentrations: 5 and 10 μM Incubation Duration: 4 days Experimental Results: Inhibition of TH17 cell differentiation in a dose-dependent manner. The cellular activity is assessed using EL4 T cells or primary mouse CD4+ T cells under TH17-skewing conditions. For EL4 cells, they are stimulated with PMA/ionomycin in the presence or absence of SR12418 (e.g., 5 microM) for 48-96 hours. IL-17A production is then measured by ELISA. For primary TH17 cell differentiation, naive CD4+ T cells are cultured under TH17 polarizing conditions (TGF-beta + IL-6 or IL-23) for 4 days. The percentage of IL-17A-producing CD4+ T cells is analyzed by flow cytometry after intracellular staining. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice induced with experimental autoimmune encephalomyelitis (EAE) [1]
Doses: 50 mg/kg Route of Administration: intraperitoneal (ip) injection; 50 mg/kg; twice (two times) daily Experimental Results: diminished disease The incidence is approximately 20% of mice. demonstrated no obvious signs of toxicity. Animal/Disease Models: PLP139-151-induced relapsing-remitting EAE (R-EAE) in SJL/J mice [1] Doses: 50 mg/kg Route of Administration: intraperitoneal (ip) injection; intraperitoneal (ip) injection. 50 mg/kg; twice (two times) daily; starting on day 18 post-immunization Experimental Results: Resulted in Dramatically diminished relapse severity compared to vehicle control. demonstrated a significant reduction in the frequency and number of CD4+ and CD8+ effector cells (CD44hi). In a mouse model of relapsing-remitting EAE, female SJL/J mice are immunized with PLP139-151 peptide/CFA to induce EAE. Mice are scored daily for clinical signs of disease. SR12418 is dissolved in a vehicle (e.g., 5% DMSO, 30% Kolliphor HS15, 65% saline) and administered intraperitoneally (i.p.) at a dose of 50 mg/kg twice daily, starting either at the time of immunization (preventative protocol) or at day 18 post-immunization (intervention protocol). Clinical scores are monitored to assess the compound's ability to prevent or reverse disease progression. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic parameters for SR12418 are not detailed. As a synthetic small molecule with in vivo activity, it is designed to have suitable properties for systemic administration. In the EAE studies, it is administered via intraperitoneal injection, which provides good bioavailability. Its half-life and tissue distribution properties would be consistent with its use as a research tool in acute and chronic disease models.
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| Toxicity/Toxicokinetics |
Specific toxicological data for SR12418 are not detailed. As a REV-ERB ligand, its primary pharmacodynamic effects on circadian rhythm and metabolism could lead to potential toxicities. Since it is a research-grade chemical, no extensive toxicology package (e.g., safety pharmacology, genotoxicity) is publicly available. Its use in mice at the reported dose (50 mg/kg i.p.) is described as not causing apparent adverse effects in the EAE model.
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| References | |
| Additional Infomation |
SR12418 is a research-grade chemical tool for studying the REV-ERB nuclear receptors. It is a valuable tool for the “chemical biology” of the circadian clock, allowing researchers to manipulate circadian gene expression and study its effect on TH17 cell differentiation and autoimmunity. As of the latest updates, it is not a clinical drug candidate and is used exclusively for in vitro and in vivo pre-clinical research.
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| Molecular Formula |
C31H30FNO3
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| Molecular Weight |
483.57
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| Exact Mass |
483.22
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| CAS # |
1801185-08-9
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| PubChem CID |
91820666
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| Appearance |
White to off-white solid powder
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| LogP |
6.9
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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 |
6
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| Heavy Atom Count |
36
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| Complexity |
730
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O(C(C)(C)C)C1C=CC(=CC=1)OC[C@@H]1CC2C(=CC=C(C=2)F)CN1C(C1=CC=CC2C=CC=CC1=2)=O
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| InChi Key |
JIWBEKKHQWSDNN-VWLOTQADSA-N
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| InChi Code |
InChI=1S/C31H30FNO3/c1-31(2,3)36-27-15-13-26(14-16-27)35-20-25-18-23-17-24(32)12-11-22(23)19-33(25)30(34)29-10-6-8-21-7-4-5-9-28(21)29/h4-17,25H,18-20H2,1-3H3/t25-/m0/s1
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| Chemical Name |
[(3S)-6-fluoro-3-[[4-[(2-methylpropan-2-yl)oxy]phenoxy]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-naphthalen-1-ylmethanone
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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 | 2.0680 mL | 10.3398 mL | 20.6795 mL | |
| 5 mM | 0.4136 mL | 2.0680 mL | 4.1359 mL | |
| 10 mM | 0.2068 mL | 1.0340 mL | 2.0680 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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