What Is Acadesine
AICAR is an AMPK activator, mainly used in treating acute lymphoblastic leukemia, but it may also have applications in other diseases such as diabetes. It is also a nucleoside analog capable of accessing the nucleoside pool, significantly increasing adenosine levels during ATP breakdown. Bulk AICAR can regulate glucose and lipid metabolism and inhibit the production of pro-inflammatory cytokines and iNOS. Xi'an Sonwu sells AICAR powder now; if you feel Interested, please feel free to contact Xi'an Sonwu.
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What Is AMPK
AMPK is an AMP-dependent protein kinase, a key molecule in regulating biological energy metabolism, and the core of researching diabetes and other related metabolic diseases. It is present in a variety of metabolic organs. It can be activated by a variety of stimuli in the body, including cellular stress, exercise, and hormones, as well as substances that affect cellular metabolism. Genetic and pharmacological studies have shown that AMPK is required for the body to maintain glucose balance. Due to the complex molecular mechanism, activating AMP by drug molecules is a great challenge, but its activation can improve the metabolic imbalance caused by type II diabetes.
AMPK plays a crucial role in cellular energy regulation, promoting ATP production and inhibiting ATP consumption pathways in various tissues. AMPK occurs as a heterotrimeric complex containing a catalytic alpha subunit and regulatory beta and gamma subunits. Upon binding of AMP to the γ subunit, the complex is allosterically activated, making it a more readily phosphorylated substrate at threonine 172, which is more readily phosphorylated by the major upstream AMPK kinase LKB1 in the activation loop of the α subunit. This kinase is activated in response to stress that depletes the cellular ATP supply. The combination between AMP and the gamma subunit allosterically activates the complex, making AMPK a substrate for the upstream AMPK kinase LKB1.
AMPK is the primary regulator of lipid metabolism and glucose metabolism. AMP-dependent protein kinase is a crucial molecule in regulating biological energy metabolism and is the core of research on diabetes and other metabolic-related diseases. In many species, AMPK can act as an essential regulator of senescence by interacting with mTOR and sirtuins. As it is a central lipid and glucose metabolism regulator, AMPK is considered a critical therapeutic target for treating obesity, and type II diabetes.
What Are the Functions of AMPK
1. Inhibits anabolism
In times of energy scarcity, AMPK inhibits multiple biosynthetic pathways. The first demonstrated signaling pathway inhibits lipid and sterol synthesis, the rate-limiting step in cholesterol synthesis, by inhibiting ACC1, ACC2, and phosphorylated β-reductase. Therefore, AMPK can treat related diseases caused by fatty acids. AMPK re-regulates metabolism through transcriptional regulation of biosynthesis. In addition to this, AMPK also binds proteins by phosphorylating sterol regulatory elements and regulates metabolism at the transcriptional level.
2. Promote the synthesis of mitochondria
Mitochondria are synthesized to increase energy output, producing more ATP. Exercise and muscle activity induce mitochondria synthesis and increase muscles' oxidative capacity. This operation proves that exercise is also an effective AMPK activator, and long-term activation of AMPK can increase the synthesis of mitochondria. In addition, the AMPK activator Acadesine can act as an exercise mimetic agent. The effect of AMPK on synthetic mitochondria is crucial for exercise and muscle mitochondria and has therapeutic implications in various pathological conditions.
3. Regulate autophagy
Autophagy is the process by which a specialized organelle recycles components such as proteins, macromolecules, organelles, and pathogens. The autophagosome consists of several multiprotein complexes that control each reaction step, and AMPK can regulate this organelle in numerous ways.
AMPK has been shown to regulate autophagy in yeast and mammalian cells. Its molecular characterization revealed that AMPK regulates autophagy at different stages. First, AMPK directly phosphorylates sites four at Thr1227 and Ser1345 of TSC2, an upstream regulator of mTOR, and locations 5 at Ser722 and Ser792 of the mTORC1 subunit PASTOR. Both of these phosphorylation processes are involved in reducing mTOR activity under conditions of energy stress. As mentioned above, the reduction of mTOR activity alleviated the inhibitory phosphorylation of ULK1 and activated autophagy.
4. Transcription and regulation of autophagy
In addition to regulating general transcriptional regulators, AMPK activation can directly or indirectly regulate genes involved in metabolism, autophagy, and lysosomal functions. AMPK can directly phosphorylate the FOXO family transcription factor 20 and regulate autophagy-related genes 198. AMPK regulates lysosome synthesis through TFEB during the differentiation of embryonic stem cells into embryoid bodies. Under the above conditions, when AMPK is activated and mTOR is inhibited, TFEB dephosphorylation imports it into the nucleus, which initiates the CLEAR gene network 200. Gene products in the CLEAR gene network control lysosome activity, which autophagy requires.
AMPK is considered a key regulator of mitochondrial homeostasis, regulating all aspects of the mitochondrial life cycle, from synthesis and dynamics to mitophagy. Mitochondria are the main sites of ATP generation in cells, and AMPK, as a low ATP sensor, maintains the homeostasis of ATP and regulates downstream signaling pathways to maintain an optimal mitochondrial state. Thus, AMPK becomes the protector of mitochondria.
What Are the Functions of AICAR
AICAR drug, as an AMPK activator, can regulate glucose and lipid metabolism and inhibit the production of proinflammatory cytokines and iNOS.
1. After 30-40 minutes of using AICAR, ZMP in isolated hepatocyte extracts will increase and remain relatively stable at about four nmol/g. It causes AMPK activation in rat hepatocytes and adipocytes at 15 minutes but does not affect ATP, ADP, or AMP levels.
2. Significantly inhibited fatty acid and sterol synthesis in rat hepatocytes.
3. Causes inactivation of HMG-CoA reductase.
4. Induce apoptosis of B-CLL cells.
5. The cell viability of the patient's B-CLL cells was reduced from 68% to 26%.
6. Induction of caspase activation and cytochrome C release from mitochondria.
7. AICAR phosphorylation is to induce apoptosis.
8. Significantly reduces B cell activity but has little effect on T cell activity.
9. Causes decreased cell metabolism in K562, LAMA-84 and JURL-MK1, and can effectively kill K562 cells and Ba/F3 cells carrying the T315I-BCR-ABL mutant.
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Factory Environment
1.Xi'an Sonwu Biotech Co.,Ltd has its own factory,so it has adequate stock. Also,Xi'an Sonwu has clean and tidy producing department with advanced equipment. With the lead of Xi'an Sonwu, researchers are constantly developing new products to meet customer's need.
2.Xi'an Sonwu Biotech Co.,Ltd has advanced test equipment and professional testers, which all show that Xi'an Sonwu aims to supply accurate and effective data and good service.
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FAQ
1. How to buy products from Xi'an Sonwu?
You can contact Xi'an Sonwu via email, phone, and social media.
2. How to ensure the product quality before ordering?
Each batch of products needs to be tested to provide customers with COA and other third parties.
3. How to pack and store AICAR Powder?
Packaging: export grade sealed drum, vacuum sealed aluminum foil packaging, can also be packed according to customer needs.
Storage: please store in a cool and dry place to avoid bright light and high temperature.
If you want to buy Acadesine, feel free to contact Xi'an Sonwu.
E-mail: sales@sonwu.com
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