OB-1 is a potent stomatin-like protein-3 (STOML3) inhibitor that inhibits Piezo1 currents with an IC50 value of 10nM[1]. Inhibition of STOML3 oligomerization by OB-1 suppresses Piezo channels and reduces the sensitivity of mechanically gated currents in sensory neurons, consequently alleviating tactile allodynia[2]. OB-1 has been widely used to block Ca2+ influx in B cells and inhibit B cell responses to membrane-presented antigens[3].
In vitro, OB-1 treatment (25µM) for 48 hours significantly inhibited lipid accumulation, resulting in a reduction in lipid droplet size and an increase in the phosphorylated ERK level in 3T3-L1 cells[4].
In vivo, a single intraosseous injection of 10µl OB-1 (250pmol dissolved in 10µl saline) alleviated pain behavior induced by carrageenan injection into the tibial bone marrow cavity within 30 minutes in a rat model of acute experimental bone pain[5].
References:[1] Wetzel C, Pifferi S, Picci C, et al. Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity[J]. Nature neuroscience, 2017, 20(2): 209-218.
[2] Wang D, Tabti R, Elderwish S, et al. SFPH proteins as therapeutic targets for a myriad of diseases[J]. Bioorganic & medicinal chemistry letters, 2020, 30(22): 127600.
[3] Kwak K, Sohn H, George R, et al. B cell responses to membrane-presented antigens require the function of the mechanosensitive cation channel Piezo1[J]. Science signaling, 2023, 16(804): eabq5096.
[4] Wu S C, Lo Y M, Lee J H, et al. Stomatin modulates adipogenesis through the ERK pathway and regulates fatty acid uptake and lipid droplet growth[J]. Nature communications, 2022, 13(1): 4174.
[5] Morgan M, Thai J, Nencini S, et al. Stomatin-like protein 3 modulates the responses of Aδ, but not C fiber bone afferent neurons to noxious mechanical stimulation in an animal model of acute experimental bone pain[J]. Molecular Pain, 2023, 19: 17448069231222407.