AMPK (AMP-activated protein kinase) plays a pivotal role in the regulation of cellular energy homeostasis as the principal energy sensor in most eukaryotic cells. In response to stress, AMPK activation switches on catabolic pathways that generate ATP while simultaneously inactivating biosynthetic pathways that consume ATP.
AMPK Activadores/Inhibidores (AMPK Activators/Inhibitors)
Productos selectivos de isoformas
| Nº Cat. | Nombre del producto | Información | Citas de uso del producto | Validaciones del producto |
|---|---|---|---|---|
| S7306 | Dorsomorphin Dihydrochloride | Dorsomorphin 2HCl es un potente, reversible y selectivo inhibidor de AMPK con un Ki de 109 nM en ensayos sin células, sin mostrar una inhibición significativa de varias quinasas estructuralmente relacionadas, incluyendo ZAPK, SYK, PKCθ, PKA y JAK3. También inhibe la actividad del receptor de BMP tipo I. La Dorsomorphin induce autophagy en líneas celulares de cáncer. |
|
|
| S1208 | Doxorubicin (Adriamycin) Hydrochloride | Doxorubicin (DOX) HCl es un agente antibiótico que inhibe la DNA topoisomerase II humana con una IC50 de 2,67 μM. La Doxorubicin reduce la fosforilación basal de AMPK. La Doxorubicin se usa en el tratamiento concomitante de pacientes infectados por el HIV, pero se ha encontrado que tiene un alto riesgo de reactivación del VHB.Este producto puede precipitar cuando se disuelve en solución de PBS. Se recomienda preparar la solución madre en agua pura y diluirla con agua pura o solución salina para obtener la solución de trabajo.Doxorubicin (Adriamycin) HCl se puede usar para inducir modelos animales de enfermedad renal. |
|
|
| S1950 | Metformin Hydrochloride | Metformin Hydrochloride (Clorhidrato de 1,1-dimetilbiguanida) es un Agente Antihiperglucémico altamente eficaz, que disminuye principalmente la hiperglucemia en los hepatocitos al suprimir la gluconeogénesis hepática (producción de glucosa por el hígado). También promueve la Mitophagy en células mononucleares e induce la apoptosis de células de cáncer de pulmón a través de la activación de la vía JNK/p38 MAPK y GADD153. |
|
|
| S8161 | ON123300 | ON123300 es un potente inhibidor de quinasas de múltiples dianas con IC50 de 3,9 nM, 5 nM, 26 nM, 26 nM, 9,2 nM y 11 nM para CDK4, Ark5/NUAK1, PDGFRβ, FGFR1, RET (c-RET) y Fyn, respectivamente. |
|
|
| S1396 | Resveratrol (trans-Resveratrol) | El Resveratrol tiene un amplio espectro de dianas, incluyendo las ciclooxigenasas (es decir, COX, IC50=1.1 μM), las lipooxigenasas (LOX, IC50=2.7 μM), las quinasas, las sirtuinas y otras proteínas. Tiene efectos anticancerígenos, antiinflamatorios, hipoglucemiantes y otros efectos cardiovasculares beneficiosos. El Resveratrol induce la mitofagia/autofagia y la apoptosis dependiente de la autofagia. |
|
|
| S7840 | Dorsomorphin (Compound C) | La Dorsomorfina es un potente inhibidor reversible y selectivo de la AMPK con un Ki de 109 nM en ensayos sin células, sin exhibir una inhibición significativa de varias quinasas estructuralmente relacionadas, incluyendo ZAPK, SYK, PKCθ, PKA y JAK3. La Dorsomorfina inhibe selectivamente los receptores ALK2, ALK3 y ALK6 de tipo I de BMP. La Dorsomorfina se utiliza para promover la diferenciación celular específica e inducir la autofagia de líneas celulares cancerosas. Para pruebas celulares, se recomienda la S7306 Dorsomorphin 2HCl hidrosoluble. |
|
|
| S1802 | AICAR (Acadesine) | AICAR (Acadesina, NSC105823, AICA Riboside), un activador de AMPK, da como resultado la acumulación de ZMP, que imita el efecto estimulante de AMP sobre AMPK y AMPK quinasa. Este compuesto induce mitophagy. Fase 3. |
|
|
| S2697 | A-769662 | A-769662 es un potente activador reversible de AMPK con un EC50 de 0,8 μM en ensayos libres de células, con poco efecto sobre la actividad GPPase/FBPase. |
|
|
| S5958 | Metformin (1,1-Dimethylbiguanide) | Metformin (1,1-dimetilbiguanida), un fármaco ampliamente utilizado para el tratamiento de la diabetes tipo 2, activa la proteína quinasa activada por AMP (AMPK) en hepatocitos. Metformin promueve la mitophagy en células mononucleares. Metformin induce la apoptosis de células de cáncer de pulmón a través de la activación de la vía JNK/p38 MAPK y GADD153. |
|
|
| S7898 | GSK621 | GSK621 es un activador específico y potente de AMPK. |
|
|
AMPK exists as a heterotrimeric protein complex composed of a catalytic α-subunit (α1 or α2) and regulatory β-subunit (β1 or β2) and γ- subunit (γ1, γ2 or γ3). The structure of the α-subunit consists of a conventional Ser/Thr kinase domain at the N-terminal, an auto-inhibitory domain (AID), an extended linker peptide and the α-subunit C-terminal domain (α-CTD). The β-subunit contains a carbohydrate-binding module (CBM), with the β-subunit C-terminal domain (β-CTD) interacting with both the α-CTD and the amino terminus of the γ-subunit, thus forming the core of the complex. The γ-subunit includes four tandem repeats of a sequence motif, termed a CBS repeat (cystathionine β-synthase, CBS1-4), that forms a flattened disk with one repeat in each quadrant to create four potential ligand binding sites in the centre (site 1-4). AMPK activity increases more than 100-fold when the conserved Thr172 residue in the activation loop of the catalytic α-subunit is phosphorylated by upstream AMPK kinases (AMPKK) such as LKB1 requiring the change in AMP or ADP levels, and CaMKKβ (CaMKK2) in response to increases in cell Ca2+. AMP binding to ligand binding site 1 of the γ subunit allosterically activates the AMPK complex by facilitating the phosphorylation of Thr172 in the catalytic α-subunit, whereas binding of AMP or ADP to site 3 modulates the phosphorylation state of Thr172. In addition to allosteric activation by AMP, the effects on phosphorylation and dephosphorylation of Thr172 can also be produced by ADP, which requires N-terminal myristylation of the β-subunit. [1][2]
AMPK is activated by various types of metabolic stress (glucose deprivation, hypoxia, ischemia, metabolic poisons, or muscle contraction), as well as drugs and xenobiotics (metformin, resveratrol, or berberine) through the classical or canonical mechanisms, which involve increases in cellular AMP, ADP or Ca2+. The metformin for the treatment of people with type 2 diabetes indirectly activates AMPK by increasing cellular AMP and ADP, usually by inhibiting mitochondrial ATP synthesis. Additionally, AMPK activated by resveratrol or metformin upregulates genes involved in oxidative metabolism and oxidative stress resistance by regulating transcription factors of the abnormal dauer formation 16 (DAF-16)/forkhead box O (FOXO) family, contributing to its effects on extending healthy lifespan. Some types of cellular stress such as reactive oxygen species (ROS) and DNA damaging agents (etoposide, doxorubicin and ionizing radiation) activate AMPK by non-canonical mechanisms that involve ATM rather than the increases in AMP, ADP or Ca2+ levels. Activation of AMPK enhances both the transcription and translocation of GLUT4, resulting in an increase in insulin-stimulated glucose uptake. In LKB1-knockout but not AMPKα1-knockout mice, the effects of both AICAR and contraction on glucose uptake are lost. In addition, AMPK also stimulates other catabolic processes such as fatty acid oxidation and glycolysis via inhibition of ACC2 and activation of PFKFB. AMPK is also involved in the regulation of mitochondrial biogenesis through the activation of PGC1α, and the turnover of mitochondria via the special form of autophagy termed mitophagy by activating ULK1, and subsequently triggering autophagy. In addition, mTOR complex-1 (TORC1) can be inhibited by AMPK mediated phosphorylation of both its upstream regulator, TSC2, and the TORC1 subunit Raptor. Consistent with its role in cellular energy homeostasis, AMPK also conserves ATP by switching off almost all anabolic pathways, including the biosynthesis of lipids, carbohydrates, proteins and ribosomal RNA. Moreover, AMPK also functions beyond metabolism through regulation of the cell cycle and modulation of membrane excitability. As LKB1 is a tumor suppressor and is frequently mutated in spontaneous cancers, AMPK-activating drugs such as metformin or A-769662 significantly protect against the development of cancer. [1][2]
Los productos son solo para uso de investigación. No para uso humano. No vendemos a pacientes.
©Copyright 2013 Selleck Chemicals. Todos los derechos reservados.