Sophoranone

Sophoranone ((-)-Sophoranone; Sophoranon) is an orally active competitive inhibitor of CYP2C9 (IC₅₀ = 0.966 μM) and CYP3A4. Sophoranone is a prenylated flavonoid isolated from the roots of Sophora subprostrata. Sophoranone induces apoptosis by increasing reactive oxygen species (ROS) and opening the mitochondrial channel, while upregulating myogenic genes to promote muscle regeneration. Sophoranone can be used for research on asthma, leukemia, and paralytic strabismus^{[1][2][3][4][5][6]}. In Vitro:Sophoranone ((-)-Sophoranone; Sophoranon) (4 days) inhibits the growth of human leukemia U937 (IC₅₀ = 3.8 μM) cells and human gastric cancer cells MKN7 (IC₅₀ = 1.2 μM) and AZ-521 (IC₅₀ = 6.8 μM)^[2].
Sophoranone potently and reversibly inhibits CYP2C9 enzyme activity in human liver microsomes (HLMs) in a competitive manner, with an IC₅₀ of 0.966 µM and a K_i of 0.503 µM for CYP2C9-induced tolbutamide 4-hydroxylation, while exhibiting weak or no inhibition against other tested CYP isoforms^[3].
Sophoranone (10-50 µM; 2 h) exhibits extremely low bidirectional permeability in Caco-2 cells^[3].

Sophoranone (0.5-100 μM; 30 min) exhibits potent competitive inhibition of CYP3A4 in human liver microsomes, with an IC₅₀ of 3.98 μM and a K_i of 2.17 μM for bufalin 5′-hydroxylation, and its inhibitory activity against CYP3A4 is superior to that against CYP2C19, CYP1A2, and CYP2C9^[6].
Sophoranone (5-10 µM; 6-48 h) significantly promotes cell proliferation in C2C12 cells^[5].
Sophoranone (5-10 µM; 3 days) promotes cell differentiation and fusion in C2C12 cells and upregulates Myh3, Myog, and MCK gene and protein expression^[5].

Sophoranone (up to 50 µM; 3 h-2 days) induces apoptosis in U937, HL-60, AZ-521, COLO 320DM cells and normal monocytes^[2].
Sophoranone (30 µM; 0.5-4 h) inhibits ERK1/2 and p38 kinase phosphorylation, increases caspase-3-like enzyme activity, and induces procaspase-3 cleavage activation in U937 cells^[2].
Sophoranone (20-30 µM; 6 h-1 day) increases DNA degradation without altering cell cycle distribution in U937 cells^[2].
Sophoranone (50 µM; 20 min-2 h) promotes superoxide anion production and transient hydrogen peroxide generation in U937 cells^[2].
Sophoranone (30 µM; up to 10 min) induces mitochondrial permeability transition pore (PTP) opening in mitochondria isolated from mouse liver^[2].

Sophoranone (30 µM; 0.5-4 h) promotes the release of cytochrome c from mitochondria in U937 cells and mitochondria isolated from mouse liver^[2].
Sophoranone (5-10 μM; 24 h) maintains cell survival in C2C12 cells without inducing apoptosis or altering ROS levels and the cell cycle^[5]. In Vivo:Sophoranone ((-)-Sophoranone; Sophoranon) (10 μM; subconjunctival injection; once daily; 3 days) upregulates myogenic differentiation markers and promotes regeneration and repair of injured extraocular muscles in a New Zealand rabbit model of acute medial rectus muscle crush injury^[5].
Sophoranone (75 mg/kg; o.p.; single administration; 480 min) does not significantly interfere with the in vivo pharmacokinetics of Diclofenac (HY-15036) in normal Sprague-Dawley male rat models^[3].