SR 8278
目录号 : GC15275
SR 8278是一种核受体REV-ERBα的拮抗剂，能够抑制REV-ERBα的转录，EC50 值为0.47μM。
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.
SR 8278是一种核受体REV-ERBα的拮抗剂，能够抑制REV-ERBα的转录，EC50 值为0.47μM[1]。SR 8278能够用于调节生物体内代谢，研究生物节律，还能够用于治疗帕金森病引起的情绪障碍[2, 3]。SR 8278能够通过靶向抑制NR1D1有效增强时差小鼠的泪液分泌功能[4]。
在体外，SR 8278（50μM）预处理HaCaT角质形成细胞24h，可保护角质形成细胞免受UVB辐射的伤害，但能够使角质形成细胞对UVA辐射敏感并产生活性氧[5]。
在体内，SR 8278（20μg/只小鼠）通过微量缓慢注射到中脑腹侧被盖区（VTA）治疗帕金森病小鼠，恢复了小鼠表现出的情绪相关行为缺陷，恢复了REV-ERBα和NURR1的结合活性[3]。SR 8278（5mg/kg）通过腹腔注射治疗缺血-再灌注（IR）诱发的急性肺损伤（ALI）大鼠，完全消除了SR9009在IR-ALI中的保护作用，逆转了SR9009减少肺水肿、抑制支气管肺泡灌洗液（BALF）中炎症因子生成、减少肺组织中核NF-κB p65的积累等保护机制[6]。
| 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 | |
| 化学名 | (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 | ||
| 分子式 | C18H19NO3S2 | 分子量 | 361.48 |
| 溶解度 | ≤15mg/ml in ethanol;≤10mg/ml in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7664 mL | 13.832 mL | 27.664 mL |
| 5 mM | 0.5533 mL | 2.7664 mL | 5.5328 mL |
| 10 mM | 0.2766 mL | 1.3832 mL | 2.7664 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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- Purity: >99.50%
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