GSK205 is a potent and selective TRPV4 antagonist with an IC50 value of 4.19 μM for inhibition of TRPV4-mediated Ca2+ influx[1][2].Acting at a concentration of 5 μM for 4 days, GSK205 leads to an increase in the expression of thermogenic genes, such as for example Mcp1, Mip1α, Mcp3, Rantes, and Vcam, and is accompanied by a decrease in pro-inflammatory gene programs[1].
GSK205 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Astrocytes
5 nM
Evaluate the inhibitory effect of GSK205 derivatives in primary cells expressing TRPV4. Compound 16-8 was significantly more effective than the parent molecule GSK205.
Sci Rep. 2016 Jun 1;6:26894
Articular chondrocytes
5 nM
Evaluate the inhibitory effect of GSK205 derivatives in primary cells expressing TRPV4. Compound 16-8 was significantly more effective than the parent molecule GSK205.
Sci Rep. 2016 Jun 1;6:26894
human periodontal ligament cells (hPDLCs)
30 µM
8 hours
To investigate the inhibitory effect of GSK205 on the TrPV4 channel and its impact on mechanotransduction in hPDLCs. Results showed that GSK205 treatment reduced intracellular calcium concentration and suppressed the increased expression of COX2, RANKL, and OPG induced by mechanical loading.
Mol Med Rep. 2020 May;21(5):2113-2122
N2a cells
5 μM
5 minutes
Evaluate the inhibitory effect of GSK205 derivatives on TRPV4-mediated Ca++ influx. Compounds 16-8 and 16-19 showed the strongest inhibitory effects, almost completely eliminating Ca++ influx.
Sci Rep. 2016 Jun 1;6:26894
GSK205 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Functional spine unit (FSU) culture model
Added to the culture medium
10 μM
24 hours of sustained loading
TRPV4 inhibition mitigated the changes in inflammatory cytokines, protected against IVD degeneration, but could not prevent ECM disorganization due to mechanical damage in the annulus fibrosus.
FASEB J. 2023 Feb;37(2):e22714
Mice
Trigeminal irritant pain model
Intraperitoneal injection
10 mg/kg
Single dose, observed for 45 minutes
Evaluate the effect of GSK205 derivatives in the trigeminal irritant pain model. Compounds 16-8 and 16-19 significantly reduced pain behavior in the delayed phase, while GSK205 was ineffective.
Sci Rep. 2016 Jun 1;6:26894
GSK205 动物研究
Animal study
GSK205 has a short half-life of 2 hours in plasma and adipose tissue. Administered intraperitoneally twice daily for 4 weeks at a dose of 10 mg/kg, GSK205 significantly increased the expression of thermogenic genes such as Ucp1, Pgc1a, Cidea, and Cox8b in animals. GSK205 treatment reduced the expression of pro-inflammatory chemokines, macrophage markers, and Tnfa in adipose of EPIs. GSK205 can significantly improve glucose tolerance in diet-induced obesity (DIO) mice without obvious signs of illness or weight loss[1].
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