CKD-712
CKD-712 is an orally active multi-target tetrahydroisoquinoline derivatived and a potent inhibitor of the NF-κB pathway. CKD-712 selectively inhibits MMP-9 with no effect on MMP-2, downregulates the expression of TNF-α, IL-6, cyclin A, cyclin B, CDK-1 and other proteins, and activates the PI3K/Akt signaling pathway. CKD-712 blocks the activation and nuclear translocation of NF-κB, downregulates inflammatory factors and pro-tumor metastatic proteins, and induces G2/M phase arrest in tumor cells and thereby inhibits the invasion of cancer cells. CKD-712 can be used for the research of sepsis, myocardial ischemia-reperfusion injury and non-small cell lung cancer.
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- No. CAS: 626252-75-3
- Fòrmula: C20H19NO2
- Peso molecular:305.37
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Almacenamiento:
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Actividad biológica
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NF-κB |
MMP-9 |
IL-6 |
Cdk1/cyclin B |
CDK1/cyclin A |
PI3K |
Akt |
CKD-712 (5-30 μg/mL; 48 h) dose-dependently suppresses proliferation of A549 human lung adenocarcinoma cells, with 30 μg/mL inhibiting proliferation by 60% without inducing cell death[2].
CKD-712 (30-50 µg/ml; 48 h) induces G2/M cell cycle arrest in A549 cells[2].
CKD-712 (30 µg/ml; 48 h) suppresses cyclin A, cyclin B and CDK-1 expression in A549 human lung cancer cells[2].
CKD-712 (30 µg/ml; 48 h) dose-dependently inhibits mitosis in A549 human lung carcinoma cells[2].
CKD-712 (20 µg/ml; 12 h, 24 h) inhibits adenocarcinoma cell growth[2].
CKD-712 (10 µg/ml; 1 h; pre-incubation) inhibits TNF-α-induced NF-κB activation in A549 human lung carcinoma cells[2].
CKD-712 (5-30 µg/ml; 24 h) suppressed proteins involved in proliferation, anti-apoptosis, and angiogenesis in A549 human lung carcinoma cells[2].
CKD-712 (30 µg/ml; 48 h) dose-dependently inhibits MMP-9 activity in A549 human lung carcinoma cells without affecting MMP-2 activity[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A549 human lung carcinoma cells
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Concentration:5 μg/mL, 10 μg/mL, 20 μg/mL, 30 μg/mL
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Incubation Time:48 h
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Result:Significantly suppressed cell proliferation in a dose-dependent manner up to 60% at 30 μg/mL.
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Cell Line:A549 human lung carcinoma cells
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Concentration:5 μg/mL, 10 μg/mL, 20 μg/mL, 30 μg/mL
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Incubation Time:48 h
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Result:Suppressed the expression of cyclin A, cyclin B and CDK-1 proteins.
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Cell Line:A549 human lung carcinoma cells
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Concentration:5 μg/mL, 10 μg/mL, 20 μg/mL, 30 μg/mL
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Incubation Time:24 h
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Result:Inhibited TNF-α-induced NF-κB p65 nuclear translocation; suppressed proteins involved in proliferation, anti-apoptosis, and angiogenesis including Mcl-1, COX-2, XIAP, and VEGF in A549 cells.
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Cell Line:A549 human lung carcinoma cells
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Concentration:5 μg/mL, 10 μg/mL, 20 μg/mL, 30 μg/mL
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Incubation Time:24 h
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Result:Inhibited A549 cell invasion in a dose-dependent manner.
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Cell Line:A549 human lung carcinoma cells
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Concentration:20 μg/mL
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Incubation Time:12 h, 24 h
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Result:Inhibited A549 cell migration as evidenced by controlled wound closure compared to test.
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Cell Line:A549 human lung carcinoma cells
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Concentration:5 μg/mL, 10 μg/mL, 20 μg/mL, 30 μg/mL
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Incubation Time:48 h
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Result:Induced marked cell cycle changes with an increase in the fraction of cells in G2/M, indicating significant G2/M cell death.
CKD-712 (1-3 mg/kg/day; i.p.; once daily; 4 total doses) improves survival in CLP-induced polymicrobial septic mice, with a 50% survival rate observed at 1 mg/kg/day administered over 4 days[1].
CKD-712 (2.5-20 mg/kg; i.p.; two doses (24 hours and 1 hour pre-LPS)) dose-dependently reduces markers of liver and kidney injury in LPS-induced DIC rats, with the greatest reduction in GOT (117.8 U/L) and BUN (11.8 mg/dL) observed at 20 mg/kg[1].
CKD-712 (20 mg/kg; i.p.; two doses (24 hours and 1 hour pre-LPS)) protects against LPS-induced histological damage to the liver and lung in DIC rats, reducing inflammatory cell infiltration and tissue necrosis[1].
CKD-712 (1-20 mg/kg; i.p.; single dose) dose-dependently improves survival in LPS-induced septic mice, with up to 92% survival observed at 5 and 10 mg/kg when administered 30 minutes pre-LPS[1].
CKD-712 (5-20 mg/kg; i.p.; single dose; 30 min pre-zymosan) improves survival in zymosan-induced septic mice, with a 67% survival rate observed at 20 mg/kg when administered 30 minutes pre-zymosan[1].
CKD-712 (2.5-20 mg/kg; i.p.; two doses (24 hours and 1 hour pre-LPS)) dose-dependently suppresses LPS-induced systemic inflammation in DIC rats, with the greatest reduction in TNF-α (85.5 pg/mL) observed at 10 mg/kg[1].
CKD-712 (20 mg/kg; i.p.; two doses (24 hours and 1 hour pre-LPS)) inhibits LPS-induced NF-κB translocation to the nucleus in lung pneumocytes of DIC rats, reducing pro-inflammatory signaling[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR (male, 25-30 g, zymosan-induced endotoxemia sepsis model)[1]
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Dosage:5, 10, 20 mg/kg
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Administration:Intraperitoneal (i.p.) single dose; 30 min pre-zymosan
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Result:Achieved survival rates of 42%, 50%, and 67% at 5, 10, and 20 mg/kg respectively at 6 days post-zymosan (statistically significant at 20 mg/kg, p ≤ 0.05).
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Animal Model:ICR (male, 25-30 g, LPS-induced hypothermia sepsis model)[1]
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Dosage:1, 3, 10, 20 mg/kg
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Administration:Intraperitoneal (i.p.) single dose; 30 min pre-LPS
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Result:Prevented LPS-induced hypothermia, maintaining significantly higher mean rectal temperatures compared to vehicle controls at 5 and 7 hours post-LPS (p ≤ 0.05).
Enabled all groups to recover to normal temperatures by 23 hours post-LPS.
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Animal Model:ICR (male, 25-30 g, CLP-induced polymicrobial sepsis model)[1]
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Dosage:1, 3 mg/kg/day
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Administration:Intraperitoneal (i.p.) once daily; 4 total doses (2 pre-surgery, 2 post-surgery)
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Result:Improved final survival rates to 50% and 45% at 1 mg/kg/day and 3 mg/kg/day respectively, compared to 15% survival with CLP alone at 72 hours post-surgery.
Sprague-Dawley (SD) (male, 150–160 g, LPS-induced systemic inflammation Dlc model)
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Animal Model:ICR (male, 25-30 g, LPS-induced endotoxemia sepsis model)[1]
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Dosage:1, 3, 10, 20 mg/kg (4 hours post-LPS)
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Administration:Intraperitoneal (i.p.) single dose
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Result:Achieved survival rates of 33%, 40%, 40%, and 53% at 1, 3, 10, and 20 mg/kg respectively when administered 4 hours post-LPS.
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Animal Model:ICR (male, 25-30 g, LPS-induced endotoxemia sepsis model)[1]
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Dosage:2.5, 5, 10, 20 mg/kg (1 hour post-LPS)
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Administration:Intraperitoneal (i.p.) single dose
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Result:Achieved survival rates of 47%, 60%, 67%, and 67% at 1, 3, 10, and 20 mg/kg respectively when administered 1 hour post-LPS (statistically significant at 10, 20 mg/kg, p ≤ 0.05).
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Animal Model:Sprague-Dawley (SD) (male, 150-160 g, LPS-induced septic organ injury Dlc model)[1]
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Dosage:20 mg/kg
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Administration:Intraperitoneal (i.p.); two doses (24 hours and 1 hour pre-LPS)
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Result:Inhibited LPS-induced translocation of NF-κB from the cytoplasm to the nucleus of lung pneumocytes, with NF-κB remaining localized to the cytoplasm.
Reduced liver sinusoidal enlargement and inflammatory cell infiltration caused by LPS.
Reduced lung pneumocyte hypertrophy, inflammatory cell infiltration, and central necrosis caused by LPS.
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Animal Model:Sprague-Dawley (SD) (male, 150–160 g, LPS-induced systemic inflammation Dlc model)[1]
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Dosage:2.5, 5, 10, 20 mg/kg
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Administration:Intraperitoneal (i.p.); two doses (24 hours and 1 hour pre-LPS)
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Result:LPS-induced GOT, GPT, BUN, creatinine, TNF-α, and IL-6 levels were all reduced in a dose-dependent manner at 2.5, 5, 10, and 20 mg/kg respectively.
Chemical Information
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No. CAS 626252-75-3
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Peso molecular 305.37
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Fòrmula C20H19NO2
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SMILES
OC1=CC2=C([C@H](CC3=C(C=CC=C4)C4=CC=C3)NCC2)C=C1O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Park JH, et al. Effects of the anti-sepsis drug, (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CKD-712), on mortality, inflammation, and organ injuries in rodent sepsis models. Arch Pharm Res. 2011 Mar;34(3):485-94. [Content Brief]
[2]. Lee WS, et al. Synthesized tetrahydroisoquinoline alkaloid exerts anticancer effects at least in part by suppressing NF-κB-regulated proteins in A549 human lung cancer cells. Oncol Rep. 2015;33(3):1141-1146. [Content Brief]
[3]. Chae JW, et al. Development of a LC-MS/MS method for the determination of CKD-712 in rat plasma: Application to a pharmacokinetic study in rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2017;1061-1062:123-127. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CKD-712 Related Classifications
HY-114214 Related Classifications
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- CKD-712
- 626252-75-3
- CKD712
- CKD 712
- Drug Derivative
- NF-κB
- MMP
- TNF Receptor
- Interleukin Related
- Cyclin G-associated Kinase (GAK)
- CDK
- PI3K
- Akt
- NF-κB pathway inhibitor
- orally active
- A549 cells
- SD rats
- ICR mice
- LPS-induced sepsis model
- cecal ligation and puncture (CLP) model
- LPS-induced DIC model
- disseminated intravascular coagulation (DIC)
- zymosan-induced sepsis model mice
- non-small cell lung cancer
- anti-inflammatory
- anti-sepsis
- anti-thrombotic
- anti-cancer
- organ protection
- anti-apoptosis
- cell cycle arrest
- selective MMP-9 inhibition
- PI3K/Akt signaling activation
- TNF-α downregulation
- IL-6 downregulation
- Inhibitor
- inhibitor
- inhibit