GSK205 is an inhibitor of transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential ankyrin 1 (TRPA1; IC50s = 4.19 and 5.56 µM, respectively, for the rat channels).[1] It inhibits calcium influx induced by the TRPV4 agonist GSK101 (GSK1016790A; ) in whole-cell patch-clamp assays using Neuro2a neuroblastoma cells expressing TRPV4 when used at a concentration of 5 µM. GSK205 (10 µM) prevents compression-induced increases in NF-κB transcriptional activity and secreted levels of IL-6 and VEGFA, as well as inhibits compression-induced fractures, abnormal cell morphology, and fissures in the intervertebral space, in primary mouse lumbar spines when used at a concentration of 10 µM.[2]
References:
[1].Kanju, P., Chen, Y., Lee, W., et al.Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and painSci. Rep.626894(2016).
[2].Easson, G.W.D., Savadipour, A., Anandarajah, A., et al.Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral discFASEB J.37(2)e22714(2023).