Gallein

Gallein is a small inhibitor of G protein βγ (Gβγ) subunit signalling [1].

Gβγ subunits are central participants in G protein-coupled receptor (GPCR) signaling pathways. Gβγ subunits interact with receptors, G protein α subunits and downstream targets to coordinate multiple, different GPCR functions [2].

In spheroids made by LNCaP cells and grown in collagen gels, gallein at 10 µM was able to significantly counteract β-ionone-induced LNCaP cell invasiveness [1]. In human monocyte-derived macrophages, gallein effectively inhibited M1 polarization and promoted M2 polarization [3].

In castrated male NSG mice carrying subcutaneous injected LNCaP cells, intraperitoneal injection of gallein (5 mg/kg/day) inhibited β-ionone-mediated metastasis spread [1]. In a rat model of autoimmune myocarditis, gallein (10 mg/kg/day, p.o., for 21 days) effectively improved survival and cardiac function, suppressed cardiac remodeling, and further attenuated myocardial protein expression of G protein-coupled receptor kinase 2 (GRK2) as well as high mobility group box 1 (HMGB1) and its cascade signaling proteins [3].

References:

[1]. Sanz G, Leray I, Muscat A, et al. Gallein, a Gβγ subunit signalling inhibitor, inhibits metastatic spread of tumour cells expressing OR51E2 and exposed to its odorant ligand. BMC Research Notes, 2017, 10(1): 541.

[2]. Smrcka A V. G protein βγ subunits: central mediators of G protein-coupled receptor signaling. Cellular and Molecular Life Sciences, 2008, 65(14): 2191-2214.

[3]. Karuppagounder V, Bajpai A, Meng S, et al. Small molecule disruption of G protein βγ subunit signaling reprograms human macrophage phenotype and prevents autoimmune myocarditis in rats. PLoS One, 2018, 13(7): e0200697.