Structure of SR8278
CAS No.: 1254944-66-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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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 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
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 |
Tags: SR8278 | SR 8278 | SR-8278 | REV-ERB | REV-ERBα | NR1D1 antagonist | REV-ERBα antagonist | transcriptional repression | metabolism regulation | biological rhythm | Duchenne muscular dystrophy | Alzheimer's disease | 1254944-66-5
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