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.
For research use only. We do not sell to patients.
- CAS No.: 1261080-40-3
- Formula: C18H18Cl2N6OS
- Molecular Weight:437.35
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
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Akt1 0.153 μM (IC50) |
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepG2, SMMC7721, Bel7402, Huh7, LO2
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Concentration:1.25, 2.5, 5, 10, 20, 40 μM
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Incubation Time:72 h
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Result:Inhibited cell viability in a dose-dependent manner across all tested liver cancer cell lines.
Exhibited IC50 values of 10.43 μM for HepG2, 12.51 μM for SMMC7721, 7.73 μM for Bel7402, 13.32 μM for Huh7, and 62.99 μM for normal LO2 liver cells.
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Cell Line:HepG2, Bel7402
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Concentration:5, 10, 20 μM
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Incubation Time:6 h
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Result:Reduced phosphorylation of AKT downstream substrates FOXO3a and GSK-3β, while increasing phosphorylation of AKT at Ser473 and Thr308 in a dose-dependent manner.
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Cell Line:HepG2, Bel7402
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Concentration:5, 10, 20 μM
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Incubation Time:48 h
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Result:Induced apoptosis in a dose-dependent manner: at 20 μM, the proportion of apoptotic cells (sub-G1 phase) reached 59.4% in HepG2 and 53.6% in Bel7402.
Induced early apoptosis (Annexin V-positive, PI-negative) reaching 14% in HepG2 and 28.7% in Bel7402 at 10 μM.
Induced Annexin V/PI-double positive cells reaching 75.8% in HepG2 and 67.3% in Bel7402 at 20 μM.
Induced dose-dependent cleavage of caspase-3 and PARP.
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Cell Line:HepG2, Bel7402
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Concentration:5-20 μM (dose-dependent analysis); 10 μM (time-dependent analysis)
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Incubation Time:6, 12, 24 h (time-dependent analysis)
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Result:DC-120 activated the MEK/ERK pathway in a dose- and time-dependent manner, as shown by increased phosphorylation of ERK1/2 and MEK.
DC-120 reduced phosphorylation of C-Raf at Ser259 in a dose- and time-dependent manner.
DC-120-induced ERK1/2 phosphorylation was blocked by pretreatment with U0126.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/C nude (female)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.p.; daily; 21 days
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Result:Achieved tumor growth inhibitory rates of 37.5% at 10 mg/kg and 56.7% at 20 mg/kg.
Increased phosphorylation of AKT at Ser473 and Thr308, while dramatically suppressing phosphorylation of AKT downstream substrates GSK3β, FOXO3a, and PRAS40.
Increased phosphorylation of P70S6K and 4E-BP1 (mTORC1 pathway markers) and activated ERK1/2 (MAPK pathway marker).
Stimulated a substantial increase in TUNEL-positive apoptotic tumor cells at 20 mg/kg.
Caused no toxicity based on body weight measurements.
Chemical Information
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CAS No. 1261080-40-3
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Molecular Weight 437.35
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Formula C18H18Cl2N6OS
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SMILES
O=C(N[C@H](CN)CC1=C(Cl)C=C(C=C1)Cl)C2=CN=C(S2)C3=NC(NC)=NC=C3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DC-120 Related Classifications
HY-119884 Related Classifications
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