FR900359

FR900359 is a cyclic depsipeptide that has been found in A. crenata and is an inhibitor of Gα_q, Gα₁₁, and Gα₁₄ (IC₅₀s = 13.18, 10.47, and 10 nM, respectively).^1,2 It is selective for these Gα subunits over a panel of additional Gα subunits, including Gα_s and Gα_i, in bioluminescence resonance energy transfer (BRET) assays at 1 &#181M.³ FR900359 (1 &#181M) induces relaxation of precontracted isolated mouse tail arteries and inhibits platelet aggregation induced by U-46619 in washed isolated human platelets cultured with aspirin in a concentration-dependent manner.^3,4 It induces cell cycle arrest at the G₁ phase and reduces proliferation and serum-induced migration of B16 melanoma cells.³ FR900359 (2.5 &#181g/animal) inhibits airway hyperresponsiveness in a mouse model of house dust mite-induced allergic asthma.⁵

1.Fujioka, M., Koda, S., Morimoto, Y., et al.Structure of FR900359, a cyclic depsipeptide from Ardisia crenata simsJ. Org. Chem.53(12)2820-2825(1988) 2.Kukkonen, J.P.G-protein inhibition profile of the reported Gq/11 inhibitor UBO-QICBiochem. Biophys. Res. Commun.469(1)101-107(2016) 3.Schrage, R., Schmitz, A.-L., Gaffal, E., et al.The experimental power of FR900359 to study Gq-regulated biological processesNat. Commun.610156(2015) 4.Inamdar, V., Patel, A., Manne, B.J., et al.Characterization of UBO-QIC as a Gαq inhibitor in plateletsPlatelets26(8)771-778(2015) 5.Matthey, M., Roberts, R., Seidinger, A., et al.Targeted inhibition of Gq signaling induces airway relaxation in mouse models of asthmaSci. Transl. Med.9(407)eaag2288(2017)