EX229 (Synonyms: AMPK Activator 991) |
رقم الكتالوجGC31411
One-Click Copy Product Info
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EX229 ، أحد مشتقات بنزيميدازول ، هو منشط قوي وخيفي لبروتين كيناز منشط AMP (AMPK) ، مع Kds من 0.06 ميكرومتر و 0.06 ميكرومتر و 0.51 ميكرومتر لـ α1β1γ1 و α2β1γ1 و α1β2γ1 في قياس التداخل ثنائي الطبقة ، على التوالي
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1219739-36-2
Sample solution is provided at 25 µL, 10mM.
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EX229 is a benzimidazole derivative that functions as a potent allosteric agonist of AMP-activated protein kinase (AMPK)[1]. EX229 binds to AMPK with high specificity, exhibiting differential binding affinity for various isoforms: α1β1γ1 (Kd=0.06μM), α2β1γ1 (Kd=0.06μM), and α1β2γ1 (Kd=0.51μM)[2]. EX229 effectively regulates glucose transport and inhibits lipogenesis[3].
In vitro, treatment of C2C12 myotube cells with EX229 (2–25μM) for 12 hours significantly activated the AMPK signaling pathway, as indicated by a dose-dependent increase in AMPKα phosphorylation. This was accompanied by upregulation of key unfolded protein response (UPR) markers, including ATF4 and CHOP, at the protein level[4].
In vivo, daily intramuscular administration of EX229 (2.0mg/kg) for 8 weeks in a rat model of heart failure induced by coronary artery ligation significantly reversed the cardioprotective effects of Fuyu Decoction. This was demonstrated by a marked increase in left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV), along with a significant reduction in left ventricular ejection fraction (LVEF) and fractional shortening (LVFS)[5].
References:
[1] Lai YC, Kviklyte S, Vertommen D, et al. A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators. Biochem J. 2014 Jun 15;460(3):363-75.
[2] Xiao B, Sanders MJ, Carmena D, et al. Structural basis of AMPK regulation by small molecule activators. Nat Commun. 2013;4:3017.
[3] Bultot L, Jensen TE, Lai YC, et al. Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle. Am J Physiol Endocrinol Metab. 2016 Oct 1;311(4):E706-E719.
[4] Gong J, Wang L, Tao W, et al. AMPK Mediates Early Activation of the Unfolded Protein Response through a Positive Feedback Loop in Palmitate-Treated Muscle Cells. Front Biosci (Landmark Ed). 2023 Aug 7;28(8):159.
[5] Ma J, Xu Z, Zhu J, et al. Fuyu Decoction improves ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR pathway-mediated autophagy. Nan Fang Yi Ke Da Xue Xue Bao. 2023 Mar 20;43(3):466-473.
| Cell experiment [1]: | |
Cell lines | C2C12 myotubes (mouse skeletal muscle cell line) |
Preparation Method | C2C12 myoblasts were differentiated into myotubes in high-glucose DMEM supplemented with 2% horse serum for 4 days. Myotubes were treated with EX229 at concentrations ranging from 2 to 25μM for 12 hours. |
Reaction Conditions | 2-25μM; 12 hours |
Applications | EX229 dose-dependently activated AMPK signaling, as evidenced by increased phosphorylation of AMPKα (p-AMPKα). This activation subsequently induced the unfolded protein response (UPR), marked by upregulated protein expression of UPR markers ATF4 and CHOP. EX229 also enhanced the mRNA levels of UPR-related genes, including BIP, ATF4, GADD34, and XBP1s, demonstrating EX229 role in promoting ER stress adaptation. |
| Animal experiment [2]: | |
Animal models | Male Wistar rats with heart failure induced by ligation of the left anterior descending coronary artery |
Preparation Method | Rats were treated with EX229 (2.0mg/kg) via daily intramuscular injection for 8 weeks, starting 4 weeks after heart failure induction. The treatment was combined with Fuyu Decoction (5.0g/kg, oral gavage) in the Fuyu Soup+EX229 group. |
Dosage form | 2.0mg/kg; i.m. |
Applications | EX229 administration significantly reversed the cardioprotective effects of Fuyu Decoction, exacerbating heart failure progression. EX229 increased left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV), reduced ejection fraction (LVEF) and fractional shortening (LVFS), and worsened ventricular remodeling indicators. EX229 also amplified myocardial infarction area, promoted cardiomyocyte apoptosis, and enhanced autophagy activation via the AMPK/mTOR pathway, as evidenced by upregulated p-AMPK, LC3-II/LC3-I, and Beclin1 expressions, and suppressed p-mTOR and p62 levels. |
References: | |
| Cas No. | 1219739-36-2 | SDF | |
| المرادفات | AMPK Activator 991 | ||
| Canonical SMILES | O=C(O)C1=CC(OC2=NC3=CC(Cl)=C(C4=CC5=C(N(C)C=C5)C=C4)C=C3N2)=CC=C1C | ||
| Formula | C24H18ClN3O3 | M.Wt | 431.87 |
| الذوبان | DMSO : 5.4 mg/mL (12.50 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3155 mL | 11.5776 mL | 23.1551 mL |
| 5 mM | 463.1 μL | 2.3155 mL | 4.631 mL |
| 10 mM | 231.6 μL | 1.1578 mL | 2.3155 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 3 reference(s) in Google Scholar.)