Solenopsin

Solenopsin ((-)-Solenopsin A) is an ATP-competitive and selective Akt-1 inhibitor with an IC₅₀ of 5-10 μM, and also acts as an RSK1 inhibitor. Solenopsin inhibits the activities of PDK1 in lipid rafts, downregulates PI3K, blocks PI3K-dependent generation of 3-phosphoinositides, and suppresses the phosphorylation of FOXO1a. Solenopsin induces Mitophagy and ROS production, reduces mitochondrial oxygen consumption, and exhibits antiproliferative and antiangiogenic activities. Solenopsin can be used in research related to hyperproliferative skin diseases and malignant diseases^[1][2]. IC50 & Target:IC50: 10 μM^[1]. In Vitro: Solenopsin (10 μM; 24 h) potently inhibits proliferation of human A375 melanoma, human A2058 melanoma, and murine SVR angiosarcoma cells, with activity equivalent to its enantiomer (+)-solenopsin A and greater than cis isomer or long side-chain analogs^[1].
Solenopsin (10-20 μM; 1 h) inhibits PDGF-induced Akt activity and PDK1 activation in membrane rafts of murine embryonic NIH3T3 fibroblast cells, with full inhibition at 20 μM for 1 hour and partial inhibition at 10 μM for 1 hour^[1].
Solenopsin (10 μM; 24 h) upregulates p-Akt ^S473 and p-MAPK 44/42 in human A375 and A2058 melanoma cells, while downregulating these phosphorylated proteins in murine SVR angiosarcoma cells, demonstrating a context-dependent effect based on p53 status^[1].
Solenopsin (10 μM; 24 h) reduces mitochondrial oxygen consumption rate in human UM-SCC1A squamous carcinoma cells^[1].
Solenopsin (10 μM; 18 h) induces mitophagy in human UM-SCC1A squamous carcinoma cells^[1].
Solenopsin (10 μM; 24 h) elevates reactive oxygen species levels by 1.7-2.3 fold in human A375 melanoma and murine SVR angiosarcoma cells^[1].
Solenopsin (10 μM) potently and selectively inhibits purified recombinant Akt1 in an ATP-competitive manner with an IC₅₀ of 5 to 10 μM at 0.1 mM ATP, while only significantly inhibiting one additional kinase (RSK1) out of 28 tested enzymes, and not inhibiting purified PI3K or PDK1^[2]. In Vivo: Solenopsin (3.75-6 μg/mL; immersion; continuous; 6 hours after fertilization until 32 hours after fertilization) inhibits embryonic angiogenic vessel development in transgenic zebrafish without disrupting vasculogenic vessel formation^[2].