| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
AMPK
Adenosine Monophosphate-Activated Protein Kinase (AMPK). [1] |
|---|---|
| ln Vitro |
In order to determine if YLF-466D can promote platelet AMPK and hence decrease aggregation, its effects on platelet AMPK and aggregation are investigated. Activation-dependent phosphorylation at Thr172 confirms that YLF-466D activates platelet AMPK. YLF-466D suppresses thrombin-induced platelet aggregation, which is consistent with this finding. The aforementioned suppression is noted in the aggregation induced by ADP, collagen, and thrombin, suggesting that YLF-466D's antiaggregatory activity is widespread and not exclusive to platelet agonists. With the greatest potency at 150 μM, all effects on AMPK and aggregation are concentration-dependent. Approximately 84, 55, and 87 μM are the IC50 values against thrombin-, ADP-, and collagen-induced aggregation, respectively[1].
In washed rat platelets, YLF-466D activated AMPK in a concentration-dependent manner (50-150 µM), as evidenced by increased phosphorylation at Thr172. [1] YLF-466D (50-150 µM) inhibited platelet aggregation induced by various agonists: thrombin (IC₅₀ ≈ 84 µM), ADP (IC₅₀ ≈ 55 µM), and collagen (IC₅₀ ≈ 87 µM). This anti-aggregatory effect was not agonist-specific. [1] The AMPK activation and aggregation inhibition by YLF-466D (150 µM) were abolished by pretreatment with the AMPK inhibitors compound C (10 µM) and ara-A (500 µM), confirming the mediation through AMPK. [1] YLF-466D treatment led to the phosphorylation (activation) of endothelial nitric oxide synthase (eNOS) at Ser1177 in platelets. [1] YLF-466D significantly elevated intracellular levels of cyclic nucleotides: cGMP and, to a lesser but significant extent, cAMP. These increases were prevented by AMPK inhibitors. [1] Consistent with elevated cGMP and cAMP, YLF-466D induced phosphorylation of Vasodilator-Stimulated Phosphoprotein (VASP) at both Ser239 (a PKG-dependent site) and Ser157 (a PKA-dependent site). This phosphorylation was also blocked by AMPK inhibitors. [1] In whole blood (a more physiologically relevant system than washed platelets), YLF-466D (50-150 µM) inhibited collagen-induced aggregation. This effect was also reversed by AMPK inhibitors. [1] |
| References | |
| Additional Infomation |
YLF-466D (3-[(3E)-3-[(4-chlorophenyl)phenylmethylene]-2,3-dihydro-2-oxo-1H-indol-1-yl]methyl]benzoic acid) is a novel olefinic indole derivative developed through structural optimization of the previous compound PT1, and is an AMPK activator. [1] Studies have shown that the antiplatelet mechanism of YLF-466D involves the activation of the AMPK/eNOS/cGMP-PKG signaling pathway and possible cGMP-mediated crosstalk, leading to increased cAMP levels and PKA activation. [1] The authors believe that YLF-466D has the potential for antiplatelet therapy, but its in vivo antithrombotic efficacy and clinical validation still need to be evaluated in future studies. [1]
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| Molecular Formula |
C₂₉H₂₀CLNO₃
|
|---|---|
| Molecular Weight |
465.93
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| Exact Mass |
465.113
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| CAS # |
1273323-67-3
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| PubChem CID |
51033997
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| Appearance |
Light yellow to yellow solid powder
|
| LogP |
6.609
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
780
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)/C(=C\2/C3=CC=CC=C3N(C2=O)CC4=CC(=CC=C4)C(=O)O)/C5=CC=C(C=C5)Cl
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| InChi Key |
BPBOVHROVFJFAH-CYYJNZCTSA-N
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| InChi Code |
InChI=1S/C29H20ClNO3/c30-23-15-13-21(14-16-23)26(20-8-2-1-3-9-20)27-24-11-4-5-12-25(24)31(28(27)32)18-19-7-6-10-22(17-19)29(33)34/h1-17H,18H2,(H,33,34)/b27-26+
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| Chemical Name |
(E)-3-((3-((4-chlorophenyl)(phenyl)methylene)-2-oxoindolin-1-yl)methyl)benzoic acid
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| Synonyms |
YLF466DC24 YLF-466D C-24YLF 466D C24 C 24
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~214.62 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1462 mL | 10.7312 mL | 21.4625 mL | |
| 5 mM | 0.4292 mL | 2.1462 mL | 4.2925 mL | |
| 10 mM | 0.2146 mL | 1.0731 mL | 2.1462 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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