ELP-004 is a small molecule inhibitor of transient receptor potential canonical (TRPC) channels, inhibits TRPC channel–mediated Ca2+ entry with high potency, preferentially inhibits inflammatory cytokine-induced pathological osteoclastogenesis.
ELP-004 potently inhibits OAG stimulated rapid Ca2+ entry in untreated TRPC3/6/7-expressing cells with IC50 of 1-2 uM, suppresses the increase in Fura2 ratios caused by subsequent additions of Sr2+ (3 mM) in both TRPC4- and TRPC5-expressing cells by 1 to 2 orders of magnitude (IC50 = 11.5 nM for TRPC5 and 172.4 nM for TRPC4).
ELP-004 is an allosteric modulator with both inhibitory and facilitatory (at higher concentrations) effects on the TRPC4 channel.
ELP-004 inhibits basal Ca2+ and related NFATc1 translocation in inflammatory cytokine-dependent osteoclastogenesis, has minimal effect on RANKL-induced osteoclastogenesis.
ELP-004 blocks TNFα-induced osteoclast fusion.ELP-004 inhibits osteoclastogenesis in human cells, ELP-004 also reduces bone erosion in a mouse model of rheumatoid arthritis.