DC-120

DC-120 is an ATP-competitive AKT inhibitor, with particular activity against AKT1 (an IC₅₀ of 0.153 μM). DC-120 functionally blocks AKT kinase activity and reduces the phosphorylation levels of FOXO3a and GSK-3β. DC-120 induces cancer cell apoptosis (apoptosis) and inhibits cancer cell proliferation. DC-120 activates the mTORC1 pathway via the Ca²⁺/calmodulin (calmodulin)/hVps34 signaling pathway. DC-120 abrogates AKT-mediated inhibition of CRAF, thereby activating the MEK/ERK MAPK pathway. DC-120 exerts anti-tumor activity in a nude mouse hepatocellular carcinoma xenograft model. DC-120 can be used for hepatocellular carcinoma-related research^[1]. In Vitro:DC-120 (0.1-1 μM) potently and selectively inhibits AKT1 kinase activity in a cell-free system, with an IC₅₀ of 0.153 μM, while exerting no significant inhibitory effect on PKA, PKC, ADCK3, CSNK1D or DYRK1B kinases^[1].
DC-120 (1.25-40 μM; 72 h) inhibits the proliferation of HepG2, SMMC7721, Bel7402 and Huh7 hepatocellular carcinoma cells in a dose-dependent manner, with IC₅₀ values ranging from 7.73 to 13.32 μM. It exhibits selectivity over normal LO2 hepatocytes (IC₅₀ 62.99 μM), exerts growth inhibitory effects in an AKT-dependent manner, and shows stronger activity in PTEN-deficient cells^[1].
DC-120 (5-20 μM; 0-24 h) activates the mTORC1 pathway in HepG2 and Bel7402 hepatocellular carcinoma cells via an AKT inhibition-dependent increase in intracellular Ca²⁺ levels; this elevation of Ca²⁺ enhances the phosphorylation of P70S6K and 4E-BP1 through the Ca²⁺/CaM/hVps34 axis^[1].
DC-120 (5-20 μM; 6-24 h) activates the MEK/ERK MAPK pathway in HepG2 and Bel7402 hepatocellular carcinoma cells by reducing the inhibitory phosphorylation of C-Raf at the Ser259 site^[1].
DC₅₀-120 (5-20 μM; 6-48 h) inhibits AKT pathway signaling by reducing the phosphorylation levels of FOXO3a and GSK-3β (while increasing the phosphorylation levels of AKT Ser⁴⁷³/Thr³⁰⁸), and induces dose-dependent apoptosis in HepG2 and Bel7402 hepatocellular carcinoma cells^[1].
Pretreatment with RAD001 (HY-10218) (1 μM; 1 h) or U0126 (HY-12031A) (20 μM; 1 h) synergistically enhances the apoptosis-inducing effect of DC-120 (10 μM; 48 h) on HepG2 and Bel7402 hepatocellular carcinoma cells, increasing the apoptosis rate by approximately 2-fold compared with DC-120 monotherapy^[1]. In Vivo:DC-120 (10-20 mg/kg, i.p.; daily administration; for 21 consecutive days) dose-dependently inhibits the growth of hepatocellular carcinoma xenografts, while regulating the AKT, mTORC1 and MAPK signaling pathways and inducing tumor cell apoptosis in vivo^[1].