Overview
- Lima, C.K. et al. (2014) Plos One 9, e99510.
Alomone Labs LASSBio-1135 inhibits TRPV1 channels expressed in C6 cells.mTRPV1-C6 cells were loaded with Fluo-3 AM. Changes in intracellular Ca2+ were detected via changes in Fluo-3 emission following agonist application. 5 minutes pre-incubation with 10 µM LASSBio-1135 (#L-190) inhibited 10 µM Capsaicin (#C-125)-evoked rise in intracellular Ca2+. Normalized fluorescence before and after application (arrow) of 10 µM Capsaicin in cells pre-incubated with none (black) or 10 µM LASSBio-1135 (gray).
Transient receptor potential (TRP) channels are important mediators of sensory signaling with significant effect on signal transduction pathways and cellular activity. TRPV is a member of the Vanilloid subfamily of TRP channels1.
LASSBio-1135, also known as CHEMBL466188, is a synthetic antagonist of TRPV1 channels and a blocker of TNF-α channels. It has an effective concentration of 0.1-100 μM and an IC50 of 588 and 642 nM for TRPV1 and TNF-α receptors respectively. LASSbio belongs to a family of imidazo[1,2-a] pyridine derivatives and was found to be an inhibitor of p38 MAPK and COX2 in vivo. However, similar results have not been shown to this day in vitro where LASSbio failed to inhibit p38 MAPK directly and only slightly inhibited COX2. LASSbio is highly effective in completely reducing hyperalgesia induced by capsaicin and inhibits capsaicin evoked currents in a concentration dependent manner. LASSbio also inhibits TNF-α production in macrophages stimulated by LPS by reducing p38 MAPK activation through a modulation of an upstream signaling pathway thus making it a possible therapeutic agent for the prevention of neuropathic and other pain2.
