SR 8278 |
Catalog No.GC15275
One-Click Copy Product Info
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SR 8278 is an antagonist of the nuclear receptor REV-ERBα that can inhibit the transcription of REV-ERBα with an EC50 value of 0.47μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1254944-66-5
Sample solution is provided at 25 µL, 10mM.
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SR 8278 is an antagonist of the nuclear receptor REV-ERBα that can inhibit the transcription of REV-ERBα with an EC50 value of 0.47μM[1]. SR 8278 can be used to regulate metabolism in vivo, study biological rhythms, and treat mood disorders caused by Parkinson's disease[2, 3]. SR 8278 can effectively enhance the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition[4].
In vitro, SR 8278 (50μM) pretreatment of HaCaT keratinocytes for 24h can protect keratinocytes from UVB radiation damage, but can make keratinocytes sensitive to UVA radiation and produce reactive oxygen species[5].
In vivo, SR 8278 (20μg/mouse) was slowly injected into the ventral tegmental area (VTA) of the midbrain to treat Parkinson's disease mice, which restored the emotion-related behavioral defects exhibited by the mice and restored the binding activity of REV-ERBα and NURR1[3]. SR 8278 (5mg/kg) was intraperitoneally injected into rats with acute lung injury (ALI) induced by ischemia-reperfusion (IR). It completely abolished the protective effect of SR9009 in IR-ALI and reversed the protective mechanisms of SR9009, including reducing pulmonary edema, inhibiting the production of inflammatory factors in bronchoalveolar lavage fluid (BALF), and reducing the accumulation of nuclear NF-κB p65 in lung tissue[6].
References:
[1] Kojetin D, Wang Y, Kamenecka T M, et al. Identification of SR8278, a synthetic antagonist of the nuclear heme receptor REV-ERB[J]. ACS chemical biology, 2011, 6(2): 131-134.
[2] Dong D, Sun H, Wu Z, et al. A validated ultra-performance liquid chromatography-tandem mass spectrometry method to identify the pharmacokinetics of SR8278 in normal and streptozotocin-induced diabetic rats[J]. Journal of Chromatography B, 2016, 1020: 142-147.
[3] Kim J, Park I, Jang S, et al. Pharmacological rescue with SR8278, a circadian nuclear receptor REV-ERBα antagonist as a therapy for mood disorders in Parkinson's disease[J]. Neurotherapeutics, 2022, 19(2): 592-607.
[4] Huang S, QI D, Pei X, et al. Transcriptomic analysis of SR8278 improving lacrimal gland dysfunction in-duced by jet lag in mice[J]. Recent Advances in Ophthalmology, 2024: 264-269.
[5] Cvammen W, Kemp M G. The REV‐ERB antagonist SR8278 modulates keratinocyte viability in response to UVA and UVB radiation[J]. Photochemistry and Photobiology, 2024, 100(6): 1864-1873.
[6] Chu S J, Liao W I, Pao H P, et al. Targeting Rev-Erbα to protect against ischemia-reperfusion-induced acute lung injury in rats[J]. Respiratory Research, 2023, 24(1): 247.
| Cell experiment [1]: | |
Cell lines | HaCaT keratinocytes |
Preparation Method | HaCaT cells were pre-treated with DMSO vehicle, SR 8278 (50μM), KS15 (50μM), or both KS15 and SR 8278 (KS+SR) for 24h before exposure to the indicated fluences of UVB radiation. MTT assays were performed 3 days later to determine relative viability. |
Reaction Conditions | 50μM; 24h |
Applications | The REV-ERB inhibitor SR 8278 protects keratinocytes against UVB radiation. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | The present study employed a randomized experimental design in which rats were assigned to one of eight groups. These included a control group that received DMSO, a drug control group that received 50mg/kg of SR9009 (i.p.), a group subjected to lung IR, and three groups that received different doses of SR9009 (12.5mg, 25mg, or 50mg/kg) along with lung IR, IR+SR8278 (5mg/kg), or IR+SR 8278 (5mg/kg)+SR9009 (50mg/kg) group. To facilitate intraperitoneal injection, SR9009 was dissolved in 0.5% DMSO and administered 60 min before inducing lung IR. In the IR + SR 8278 + SR9009 group, rats were pretreated with SR 8278 for 30min prior to SR9009 injection. Lung IR was induced by stopping ventilation and perfusion, leading to ischemia, and then maintaining the lungs in a deflated state for 40min, followed by 60min of ventilation and perfusion. In contrast, the control group received perfusate alone for 100min. |
Dosage form | 5mg/kg; i.p. |
Applications | SR 8278 abolished the protective effects of SR9009 in IR-ALI. In this model, SR9009 had previously demonstrated a dose-dependent reduction in lung edema, along with significant inhibition of TNF-α, IL-6, and CINC-1 production in BALF. Additionally, SR9009 restored suppressed IκB-α levels and reduced nuclear NF-κB p65 accumulation in lung tissues. It also mitigated IR-induced apoptosis and suppressed MAPK activation in injured lung tissue. However, SR 8278 treatment completely reversed these protective mechanisms. |
References: | |
| Cas No. | 1254944-66-5 | SDF | |
| Chemical Name | (S)-ethyl 2-(5-(methylthio)thiophene-2-carbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate | ||
| Canonical SMILES | O=C([C@H]1N(C(C2=CC=C(SC)S2)=O)CC3=CC=CC=C3C1)OCC | ||
| Formula | C18H19NO3S2 | M.Wt | 361.48 |
| Solubility | ≤15mg/ml in ethanol;≤10mg/ml in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7664 mL | 13.832 mL | 27.664 mL |
| 5 mM | 553.3 μL | 2.7664 mL | 5.5328 mL |
| 10 mM | 276.6 μL | 1.3832 mL | 2.7664 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 11 reference(s) in Google Scholar.)