BI-9774
BI-9774 is a potent, selective, and orally active AMPK activator, with EC50 values of 20.0 nM and 63.1 nM against human AMPK α1β1γ1 and AMPK α1β2γ1, respectively. BI-9774 binds to the allosteric drug and metabolite (ADaM) site and induces ACC Ser79 phosphorylation in HepG2 cells, with an EC50 of 83.2 nM. BI-9774 can be used in studies related to AMPK signaling, multiple sclerosis, and non-alcoholic fatty liver disease.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
The BI-9774 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
- CAS 番号: 1644498-53-2
- 分子式: C26H25ClN4O5S
- 分子量:541.02
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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生物活性
製品説明
IC50 & Target
[4]|
AMPK α1β1γ1 20 nM (EC50) |
AMPK α1β2γ1 63.1 nM (EC50) |
体外実験
BI-9774 (following a 1-hour incubation) potently induces the phosphorylation of ACC in human HepG2 hepatocellular carcinoma cells, with an EC50 of 83.2 nM[4].
BI-9774 (10 μM; 72 h) reduces PCAF protein abundance in pathogenic TH17 (pTH17) cells[3].
BI-9774 (1.25 or 10 μM; 2 h) increases the phosphorylation of ACC Ser79, ULK1 Ser555 and AMPKα Thr172 in undifferentiated primary mouse adipose-derived stem cells (mADSCs); no significant difference in the phosphorylation level of target proteins is observed between 1.25 μM and 10 μM[2].
BI-9774 (1.25 or 10 μM; 3 days) increases ACC Ser79 phosphorylation in mature primary mouse adipocytes. At 10 μM, BI-9774 significantly reduces Lep mRNA, but does not significantly alter lipid droplet accumulation, nuclear number, adipogenic index, or the mRNA levels of Pparg, Lpl, Plin1 and Adipoq. BI-9774 also does not significantly change UCP1, CKB and SERCA2 under either unstimulated or Isoprenaline (HY-108353)-stimulated conditions[2].
BI-9774 (1.25-10 μM; 8 days) reduces lipid accumulation, nuclear count and adipogenic index in a concentration-dependent manner during adipogenic differentiation of mADSC, and significantly decreases lipid droplet size at 10 μM; 1.25 μM BI-9774 simultaneously downregulates the mRNA levels of *Pparg*, *Lpl*, *Plin1*, *Adipoq* and *Lep*, as well as the protein levels of FAS, ACC and PLIN1[2].
BI-9774 (1.25 μM; administered from day 2 or day 4 to day 8) consistently reduces Lep mRNA during the adipocyte maturation stage; exposure starting on day 4 does not significantly alter adipogenesis, suggesting that decreased Lep expression can be dissociated from changes in adipogenesis[2].
Brief exposure to BI-9774 (1.25 μM; administered for the first 2 days followed by washout until day 8) during the initial stage of mADSC adipogenic differentiation persistently reduces lipid accumulation and adipogenic index, and decreases PPARγ protein and leptin in the culture supernatant. No sustained phosphorylation of AMPKα Thr172, ACC Ser79, or ULK1 Ser555 is detected on day 8, and ACC inhibition within the same time window cannot replicate this adipogenic phenotype[2].
BI-9774 (1.25 μM; during adipogenic differentiation) reduces intracellular TGFβ protein and increases Tgfbr2 mRNA, but does not significantly alter ERK/SMAD2/3 signaling or β-catenin nuclear translocation[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Undifferentiated primary mADSCs
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Concentration:1.25 or 10 μM
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Incubation Time:2 h
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Result:Increased p-ACCSer79, p-ULK1Ser555, and p-AMPKαThr172; no significant difference in phosphorylation was observed between 1.25 and 10 μM.
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Cell Line:Mature primary murine adipocytes
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Concentration:1.25 or 10 μM
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Incubation Time:3 days
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Result:Increased p-ACCSer79; no significant increase in p-ULK1Ser555 or p-AMPKαThr172 was observed.
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Cell Line:Differentiating primary mADSCs
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Concentration:1.25 μM
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Incubation Time:8 days
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Result:Reduced Pparg, Lpl, Plin1, Adipoq, and Lep mRNA.
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Cell Line:Differentiating primary mADSCs
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Concentration:1.25 μM
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Incubation Time:During differentiation
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Result:Reduced cellular TGFβ protein but did not significantly alter downstream ERK/SMAD signaling.
Parmacokinetics
体内実験
BI-9774 (30 mg/kg; oral gavage; once daily; 6 weeks) reduces hepatic Col1a1, Col1a2, Col4a1 and Timp1 mRNA by 61%, 59%, 55% and 55%, respectively, and decreases circulating IL-6, IL-1β and KC/GRO in AMLN diet-induced Lepob/Lepob mice, while Col5a1 mRNA and hepatic CD68+ macrophage infiltration show no significant changes[4].
BI-9774 (30 mg/kg; oral gavage; once daily; 4 weeks) impairs glucose tolerance in AMLN diet-induced Lepob/Lepob mice, accompanied by a dose-dependent decrease in plasma insulin at 15 min after glucose loading[4].
BI-9774 (1, 3, 10, or 30 mg/kg; oral gavage; single administration; 1 h before glucose challenge) dose-dependently improves glucose control in diet-induced obese male C57BL/6 mice[4].
BI-9774 (30 mg/kg; oral gavage; once daily; 6 weeks) increases the heart weight/body weight ratio by 13.3%, enhances myocardial glycogen storage and ventricular wall thickness, and dose-dependently restores Nppa and Ankrd1 expression in AMLN diet-induced Lepob/Lepob mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Lepob/Lepob (male, ~8 weeks old, fed high trans-fat/high fructose/high cholesterol AMLN diet for 14 weeks)[4]
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Dosage:3 mg/kg
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Administration:Oral gavage; once daily; for 6 weeks
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Result:Macrosteatosis worsened in 50% of mice versus 63% in the vehicle group.
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Animal Model:C57BL/6 (male, ~6 months old, diet-induced obese via 60% kcal high-fat diet for 3.5 months)[4]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; single dose
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Result:Showed a dose-dependent reduction in glucose area under the curve (AUC) relative to vehicle-treated mice, consistent with improved glucose control.
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Animal Model:Lepob/Lepob (male, ~8 weeks old, fed high trans-fat/high fructose/high cholesterol AMLN diet for 14 weeks)[4]
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Dosage:30 mg/kg
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Administration:Oral gavage; once daily; for 6 weeks
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Result:Reduced terminal liver weight by 2.5% and liver lipid by 10%.
Reduced plasma ALT significantly.
Reduced Col1a1, Col1a2, Col4a1, and Timp1 mRNA by 61%, 59%, 55%, and 55%, respectively.
Reduced circulating IL-6, IL-1β, and KC/GRO.
Did not significantly alter collagen-I immunopositive area or NAS.
Increased heart weight/body weight ratio by 13.3%, cardiac glycogen storage, and ventricular wall thickness.
化学情報
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CAS 番号 1644498-53-2
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分子量 541.02
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分子式 C26H25ClN4O5S
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SMILES
O(C1=NC=2C(N1)=CC(Cl)=C(N2)C3=CC=C(C=C3)C4=CC=C(N=S(C)(C)=O)C=C4)[C@H]5[C@@]6([C@](OC5)([C@H](O)CO6)[H])[H]
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
BI-9774 関連分類
HY-171889 関連分類
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