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Purity: ≥98%
SR8278 (SR-8278; SR 8278) is a novel, potent, synthetic and competitive Rev-Erbα antagonist with the potential for treating Duchenne muscular dystrophy (DMD). In mdx mice SR8278 increased lean mass and muscle function, and decreased muscle fibrosis and muscle protein degradation. SR8278 inhibits Rev-Erbα transcriptional repression with an EC50 of 0.47 μM. REV-ERBα is a member of the nuclear receptor superfamily that functions as a receptor for the porphoryin heme. REV-ERBα suppresses transcription of its target genes in a heme-dependent manner. SR8278 also blocks activity of Rev-Erbα agonist GSK 4112 in HEK293 cells. SR8278 increases expression of glucose-regulating genes, G6Pase and PEPCK in HepG2 cells.
| ln Vitro |
SR8278 exhibits an EC50 of 0.47μM for REV-ERBα transcriptional inhibition inhibitory activity[1].
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| ln Vivo |
In 6-OHDA-lesioned mice, SR8278 (slow microinjection; 20 μg/mouse) restores emotion-related behaviors to their circadian rhythms and has antidepressant and anxiolytic effects in a circadian time-dependent manner [1]. ??Slow microinjection (SR8278; 20 μg/mouse) enriches R/N motifs recognized by REV-ERBα and NURR1 while restoring binding activity of both proteins to the tyrosine hydroxylase promoter [1].
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| Animal Protocol |
Animal/Disease Models: 6-OHDA injured mice [1]
Doses: 20 μg/mouse Route of Administration: slow microinjection; 20 μg/mouse Experimental Results: The emotion-related behavioral defects of 6-OHDA injured mice were restored. Altered remaining DAergic neuron-specific REV-ERBα and Nurr1 transcript levels in the VTA. Restoration of REV-ERBα and NURR1 binding activity is associated with antagonistic crosstalk of TH promoter and TH protein levels in the VTA. Dawn induces enrichment of REV-ERBα and NURR1 binding motifs. |
| References |
[1]. Kojetin , et al. Identification of SR8278, a synthetic antagonist of the nuclear heme receptor REV-ERB. ACS Chem Biol. 2011 Feb 18;6(2):131-4.
[2]. Dong D, 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 Chromatogr B Analyt Technol Biomed Life Sci. 2016 May 1;1020:142-7. [3]. Jeongah Kim, et al. Pharmacological Rescue with SR8278, a Circadian Nuclear Receptor REV-ERBα Antagonist as a Therapy for Mood Disorders in Parkinson's Disease. Neurotherapeutics. 2022 Mar;19(2):592-607. |
| Molecular Formula |
C18H19NO3S2
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|---|---|
| Molecular Weight |
361.47
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| Exact Mass |
361.0806
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| CAS # |
1254944-66-5
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| Related CAS # |
1254944-66-5
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| SMILES |
O=C(C1N(C(C2=CC=C(SC)S2)=O)CC3=C(C=CC=C3)C1)OCC
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| InChi Key |
UIEBLUZPSFAFOC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19NO3S2/c1-3-22-18(21)14-10-12-6-4-5-7-13(12)11-19(14)17(20)15-8-9-16(23-2)24-15/h4-9,14H,3,10-11H2,1-2H3
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| Chemical Name |
ethyl 2-{[5-(methylsulfanyl)thiophen-2-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
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| Synonyms |
SR8278 SR 8278 SR-8278
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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 : ~100 mg/mL (~276.64 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.92 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7665 mL | 13.8324 mL | 27.6648 mL | |
| 5 mM | 0.5533 mL | 2.7665 mL | 5.5330 mL | |
| 10 mM | 0.2766 mL | 1.3832 mL | 2.7665 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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