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Chemical Structure| 1254944-66-5 Chemical Structure| 1254944-66-5

Structure of SR8278
CAS No.: 1254944-66-5

Chemical Structure| 1254944-66-5

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SR8278 is a rev-erbα antagonist. It inhibits Rev-Erbα transcriptional repression (EC50 = 0.47 μM) and blocks activity of Rev-Erbα agonist GSK 4112 in HEK293 cells. SR8278 increases expression of glucose-regulating genes, G6Pase and PEPCK in HepG2 cells.

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Product Details of SR8278

CAS No. :1254944-66-5
Formula : C18H19NO3S2
M.W : 361.48
SMILES Code : O=C(C1N(C(C2=CC=C(SC)S2)=O)CC3=C(C=CC=C3)C1)OCC
MDL No. :MFCD18782736
InChI Key :UIEBLUZPSFAFOC-UHFFFAOYSA-N
Pubchem ID :53393127

Safety of SR8278

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HepG2 cells 7.5 µM 24 h SR8278 significantly inhibited the growth of HepG2 cells PMC11494309
Hepa1-6 cells 7.5 µM 24 h SR8278 significantly inhibited the growth of Hepa1-6 cells PMC11494309
22RV1 cells 7.5 µM 24 h SR8278 significantly inhibited the growth of 22RV1 cells PMC11494309
C4-2B cells 7.5 µM 24 h SR8278 significantly inhibited the growth of C4-2B cells PMC11494309
Mouse gingival fibroblasts (mGFs) 2.5 μM To investigate whether BMAL1 regulates GSDMD-mediated pyroptosis through NR1D1, SR8278 treatment increased the protein levels of NLRP3 and CASPASE1 but decreased the expression and cleavage of GSDMD, significantly improving cell rupture and death PMC11861291
BV-2 cells 10 μM, 20 μM 24 h SR8278 increased Aβ internalization in a dose-dependent manner, with significant effects at 20 μM. PMC6996949
BV-2 cells 20 μM 24 h SR8278, by inhibiting REV-ERBα/β activity, upregulated Bmal1 expression and accelerated microglial uptake of fAβ1-42 even when lysosomal degradation was blocked. PMC6996949
NTERT keratinocytes 10 μM 24 h SR8278 enhanced BMAL1 activity and reduced HSV-1 infection. PMC10619492
Human primary keratinocytes 10 μM 24 h SR8278 treatment significantly reduced HSV-1 antigen expression in the epidermis and decreased HSV-1 viral load. PMC10619492
HepG2 cells 10 μM 24 h To evaluate the effect of SR8278 on the expression of REV-ERBα target genes G6Pase and PEPCK in HepG2 cells, results showed that SR8278 significantly increased the expression of these genes, presumably by blocking the action of the endogenous agonist heme. PMC3042041
HEK293 cells 10 μM 24 h To assess the REV-ERBα antagonist activity of SR8278 in HEK293 cells, results showed that SR8278 enhanced the expression of the reporter gene, presumably by blocking the action of the endogenous agonist heme. PMC3042041

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice GH3 xenograft tumor model Intraperitoneal injection 50 mg/kg Once daily for 10 days SR8278 significantly inhibited the growth of GH3 xenograft tumors in mice, as evidenced by lower tumor volume and weight. PMC10196825
Mice C4-2B xenograft tumor model Not specified 10 mg/kg 3 weeks SR8278 significantly inhibited tumor growth PMC11494309
Mice Model of circadian rhythm disruption and periodontitis induced by simulated shift work Intraperitoneal injection 500 μM(110 μL) Every 2 days To investigate whether SR8278 alleviates circadian disruption-aggravated periodontitis by increasing BMAL1 levels and reducing GSDMD-mediated pyroptosis. Results showed that SR8278 injection further increased BMAL1 levels, significantly reduced the N-terminal cleavage of GSDMD, and alleviated alveolar bone resorption and periodontal destruction PMC11861291
Mice Myeloid-specific Bmal1-deficient mice Intraperitoneal injection 20 mg/kg Single injection, monitored for 3 days To investigate the effect of SR8278 on noncanonical inflammasome-mediated pyroptosis and lethality. The results showed that SR8278 significantly increased poly(I:C)-stimulated SAA1 transcription and noncanonical inflammasome-mediated lethality in mice. PMC10907614
Mice 6-OHDA-lesioned Parkinson’s disease mouse model Local injection into the midbrain VTA 20 µg/mouse 3 hours before each behavioral test, continuous behavioral testing SR8278 exerted antidepressant and anxiolytic effects in 6-OHDA-lesioned mice, especially at dawn, restoring the circadian rhythm of mood-related behaviors. PMC9226214
Rats Ischemia-reperfusion-induced acute lung injury model Intraperitoneal injection 5 mg/kg Single dose, lasting 30 minutes SR8278 significantly blocked the protective effects of SR9009 against ischemia-reperfusion-induced lung injury PMC10571317

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.77mL

0.55mL

0.28mL

13.83mL

2.77mL

1.38mL

27.66mL

5.53mL

2.77mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

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