AMPK
Signaling Pathway Map
Research Area
Inhibitory Selectivity
AMPK Products
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1208 |
Doxorubicin (Adriamycin) HClDoxorubicin (Adriamycin) HCl is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage, mitophagy and apoptosis in tumor cells. Doxorubicin reduces basal phosphorylation of AMPK. Doxorubicin is used in the concomitant treatment of HIV-infected patients but is found to be at high risk of HBV reactivation. |
Cell viabilities with increasing concentrations of cisplatin (CP) and doxorubicin (DOXO) under normoxic and hypoxic condition for 48 hours were determined by MTT assay. IC50 values are presented as the means ?SDs (n=4) and * denotes p<0.05. |
|
| S1113 |
GSK690693GSK690693 is a pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 2 nM/13 nM/9 nM in cell-free assays, also sensitive to the AGC kinase family: PKA, PrkX and PKC isozymes. GSK690693 also potently inhibits AMPK and DAPK3 from the CAMK family with IC50 of 50 nM and 81 nM, respectively. GSK690693 affects Unc-51-like autophagy activating kinase 1 (ULK1) activity, robustly inhibits STING-dependent IRF3 activation. Phase 1. |
UPN cells were treated with GSK690693 or MK2206 (1 uM) for 1h followed by LPA (10 uM), EGF or IGF-1 (10 ng/ml) for another 1h and Western blot was performed. Band intensities of phospho-AKT (p-AKTS473), phospho-S6 (p-S6S240/S244), phospho-YB-1 (p-YB-1S102) and YB-1 were quantified and normalized to the intensity of ERK2. It directly determined the role of AKT using two potent, AKT inhibitors with distinct actions—a catalytic domain inhibitor, GSK690693, and an allosteric inhibitor, MK2206 -in UPN and SKOV3 cells, which showed appreciable AKT and YB-1 phosphorylation upon growth factor stimulation. GSK690693 increased basal and growth factor-induced AKT phosphorylation due to blocking a negative feedback loop downstream of AKT, whereas MK2206 abolished both basal and growth-factor-induced AKT phosphorylation.
|
|
| S7306 |
Dorsomorphin (Compound C) 2HClDorsomorphin 2HCl is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type Ⅰ BMP receptor activity. Dorsomorphin induces autophagy in cancer cell line. |
AMPK inhibition by compound C(Dorsomorphin) inhibited autophagy activation and neuroprotection induced by IPC in PC12 cells. (A) Compound C (Comp C) abolished IPC induced neuroprotection in PC12 cells. Cells were incubated with compound C 5 μM 60 min before the onset of IPC. Twelve hours after IPC, the cells were subjected to OGD for 10 h and cell viability was examined with CCK-8 kit. (B) Compound C reduced LC3II/LC3I ratio. The cells were incubated with compound C 5 μM 60 min before the onset of IPC. Then the cells were harvested 12 h after IPC and subjected to Western blot analysis. Bar represents mean ± SD, n = 3. *P < 0.05, ***P < 0.001 compared with the control group; $$$ P < 0.001 compared with the OGD group; %%% P < 0.001 compared with the IPC + OGD group; # P < 0.05 compared with the IPC group. |
|
| S7317 |
WZ4003WZ4003 is a highly specific NUAK kinase inhibitor with IC50 of 20 nM and 100 nM for NUAK1 and NUAK2 in cell-base assays, respectively, without significant inhibition on 139 other kinases. |
The AMPK inhibitor, WZ4003, and the p38 MAPK inhibitor, SB203580, could inhibit the APN-induced overexpression of CXCL1 and CXCL8 and h-JBMMSCs chemotaxis. After treated with WZ4003 and SB203580, the expression of CXCL1 (A and B) and CXCL8 (C and D) in the cells and supernatants of h-JBMMSCs treated with or without APN was evaluated by the ELISA assay (n = 3; *P < 0.05; **P < 0.01) |
|
| S7318 |
HTH-01-015HTH-01-015 is a potent and selective NUAK1 inhibitor with IC50 of 100 nM, >100-fold selectivity over NUAK2. |
Mouse BMDMs and human THP1 cells were treated with LPS (200 ng/ml) in the absence or presence of indicated AMPK activators (metformin, quercetin, resveratrol, AICAR, A-769662, and salicylate), AMPK inhibitors (compound C, WZ4003, and HTH-01-015), or HMGB1 inhibitor (glycyrrhizin) for 24 h. HMGB1 release in cell medium was assayed using ELISA kit, respectively (n = 3, *p < .05 versus LPS or Escherichia coli group).
|
|
| S7840 |
Dorsomorphin (Compound C)Dorsomorphin is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy. |
FGF21 activates myogenic and aerobic myofiber-associated genes expression via AMPK pathway. The activator (acadesine) or inhibitor (dorsomorphin) of AMPK pathway were used to treat the pcDNA3.1-21 or control transfected C2C12 myoblasts. For this experiment, four groups were set up: FGF21-ACA (pcDNA3.1-21‡acadesine), Control-ACA (control‡acadesine), FGF21-DOR (pcDNA3.1-21‡dorsomorphin), and Control-DOR(control‡dorsomorphin). The qRT-PCR was performed to detect the genes expression of FGF21 (A), AMPK (B), Sirt 1, Myoglobin(C), Desmin (D), MEF2c (E), a-actin (F). (G) The C2C12 myoblasts were transiently transfected with pCDNA3.1-21 or pCDNA3.1, Western blot showed FGF21 activated AMPK signal via FGF21-Sirt1-AMPK. For the phosphorylated AMPK (right), the intensity of band was normalized total AMPK, and then normalized by control. (H and I) FGF21, as well as AMPK activator acadesine (ACA), increased phosphorylation of AMPM, and myogenic genes expression, especially MyHC I, which was activated by ACA (FGF21‡ACA) and suppressed by AMPK inhibitor DOR(FGF21‡DOR). The data are presented as mean±SD (*P<0.05, **P<0.01, and P<0.001), n=ˆ3. |
|
| S1033 |
Nilotinib (AMN-107)Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition. |
Effect of nilotinib on Bcr-Abl kinase activity in ABCB1- and ABCG2- overexpressing CD34+CD38- cells. K562 parental cells and CD34+CD38- subpopulation isolated from K562 cells were treated with nilotinib at 0.01, 0.1 and 1.0 umol/L for 12 h. Equal amount of protein was loaded for western blot analysis as described in the Experimental section. The experiments were repeated at least three times independently, and a representative experiment is shown. |
|
| S2697 |
A-769662A-769662 is a potent, reversible AMPK activator with EC50 of 0.8 μM in cell-free assays, little effect on GPPase/FBPase activity. |
Cells were treated with CP, DOXO, SRT1720 (100 nM), EX527 (100 nM), A769662 (10 μM) and Compound C (1 μM) under normoxic or hypoxic conditions for 48 hours, and then their viabilities were measured by MTT. |
|
| S1802 |
AICAR (Acadesine)AICAR (Acadesine), an AMPK activator, results in accumulation of ZMP, which mimics the stimulating effect of AMP on AMPK and AMPK kinase. AICAR (Acadesine) induces mitophagy. Phase 3. |
Cultured hepatocytes were treated with 10 μM Compound C (Comp.C) for 30 min before treatment with 10 μM SAL, 1 mM AICAR for 3 h. Cell lysates were immunoblotted for the phosphorylation of AMPK, ACC, Akt and GSK3β. *P < 0.05, **P < 0.01 versus control; ##P < 0.01 versus SAL alone; †P < 0.05, ††P < 0.01 versus AICAR alone. Values are means ± SEM (n = 4). |
|
| S8953New |
ASP4132ASP4132 is a potent and orally active activator of Adenosine Monophosphate-Activated Protein Kinase (AMPK) with EC50 of 0.018 μM. ASP4132 is used as a clinical candidate for the treatment of human cancer. |
||
| S2542 |
Phenformin HClPhenformin HCl is a hydrochloride salt of phenformin that is an anti-diabetic drug from the biguanide class. It activates AMPK, increasing activity and phosphorylation. |
a set of RNAi-resistant rescue forms of Cdc37 plasmids were transfected into stable Cdc37-RNAi HCT116 cells. 24 h after transfection cells were treated with phenformin and then subjected to FLAG immunoprecipitation.
|
|
| S5284 |
Adenosine 5'-monophosphate monohydrateAdenosine 5'-monophosphate monohydrate (5'-AMP) is an activator of a class of protein kinases known as AMP-activated protein kinase (AMPK). |
||
| S8335 |
PF-06409577PF-06409577 is orally bioavailable AMPK activator with EC50 of 7 nM for α1β1γ1 in the TR-FRET assay and it shows no detectable inhibition of hERG in a patch-clamp assay (100 μM) and was not an inhibitor (IC50 > 100 μM) of the microsomal activities of major human cytochrome P450 isoforms. |
||
| S3832 |
EuphorbiasteroidEuphorbiasteroid, a component of Euphorbia lathyris L., inhibits adipogenesis of 3T3-L1 cells through activation of the AMPK pathway and induces HL-60 cells to apoptosis via promoting Bcl-2/Bax apoptotic signaling pathway in a dose-dependent manner. Euphorbiasteroid is a tricyclic diperpene of Euphorbia lathyris L., inhibits tyrosinase, and increases the phosphorylation of AMPK, with anti-cancer, anti-virus, anti-obesity and multidrug resistance-modulating effect. |
||
| S7898 |
GSK621GSK621 is a specific and potent AMPK activator. |
GSK621 dose-dependent activation of AMPK in erythroblasts. Western Blot analysis of PT172 AMPKα1, PS79 ACC and PS555 ULK1 in primary erythroblasts incubated for 3 h with increasing doses of GSK621. Anti-HSC70 was used as a loading control.
|
|
| S8654 |
ex229 (compound 991)EX229 (compound 991) is a potent AMPK activator that is 5-10-fold more potent than A769662 in activating AMPK. |
||
| S8803 |
MK-3903MK-3903 is a potent and selective AMPK activator with an EC50 of 8 nM for α1 β1 γ1 subunit. It activates 10 of the 12 pAMPK complexes with EC50 values in the range of 8-40 nM and maximal activation >50%. |
||
| S9096 |
ligustroflavoneLigustroflavone, isolated from the leaves of Turpinia montana, shows high antioxidant capacity and is reported to be an AMPK activator. |
||
| S7953 |
ETC-1002ETC-1002,also known as Bempedoic acid, is an orally available, once-daily LDL-C lowering small molecule designed to lower elevated levels of LDL-C and to avoid side effects associated with existing LDL-C lowering therapies.ETC-1002 is an activator of hepatic AMP-activated protein kinase (AMPK). It has potent inhibitory activity against hepatic ATP-citrate lyase(IC50=29 uM). |
||
| S4561 |
DanthronDanthron functions in regulating glucose and lipid metabolism by activating AMPK. Danthron is a natural product extracted from the traditional Chinese medicine rhubarb. Danthron used to be a laxativa and now is currently used as an antioxidant in synthetic lubricants, in the synthesis of experimental antitumor agents, as a fungicide and as an intermediate for making dyes. |
||
| S6221 |
Methyl cinnamateMethyl cinnamate, an active component of Zanthoxylum armatum, is a widely used natural flavor compound with antimicrobial and tyrosinase inhibitor activities. Methyl Cinnamate Inhibits Adipocyte Differentiation via Activation of the CaMKK2--AMPK Pathway in 3T3-L1 Preadipocytes. |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1208 |
Doxorubicin (Adriamycin) HClDoxorubicin (Adriamycin) HCl is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage, mitophagy and apoptosis in tumor cells. Doxorubicin reduces basal phosphorylation of AMPK. Doxorubicin is used in the concomitant treatment of HIV-infected patients but is found to be at high risk of HBV reactivation. |
Cell viabilities with increasing concentrations of cisplatin (CP) and doxorubicin (DOXO) under normoxic and hypoxic condition for 48 hours were determined by MTT assay. IC50 values are presented as the means ?SDs (n=4) and * denotes p<0.05. |
|
| S1113 |
GSK690693GSK690693 is a pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 2 nM/13 nM/9 nM in cell-free assays, also sensitive to the AGC kinase family: PKA, PrkX and PKC isozymes. GSK690693 also potently inhibits AMPK and DAPK3 from the CAMK family with IC50 of 50 nM and 81 nM, respectively. GSK690693 affects Unc-51-like autophagy activating kinase 1 (ULK1) activity, robustly inhibits STING-dependent IRF3 activation. Phase 1. |
UPN cells were treated with GSK690693 or MK2206 (1 uM) for 1h followed by LPA (10 uM), EGF or IGF-1 (10 ng/ml) for another 1h and Western blot was performed. Band intensities of phospho-AKT (p-AKTS473), phospho-S6 (p-S6S240/S244), phospho-YB-1 (p-YB-1S102) and YB-1 were quantified and normalized to the intensity of ERK2. It directly determined the role of AKT using two potent, AKT inhibitors with distinct actions—a catalytic domain inhibitor, GSK690693, and an allosteric inhibitor, MK2206 -in UPN and SKOV3 cells, which showed appreciable AKT and YB-1 phosphorylation upon growth factor stimulation. GSK690693 increased basal and growth factor-induced AKT phosphorylation due to blocking a negative feedback loop downstream of AKT, whereas MK2206 abolished both basal and growth-factor-induced AKT phosphorylation.
|
|
| S7306 |
Dorsomorphin (Compound C) 2HClDorsomorphin 2HCl is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type Ⅰ BMP receptor activity. Dorsomorphin induces autophagy in cancer cell line. |
AMPK inhibition by compound C(Dorsomorphin) inhibited autophagy activation and neuroprotection induced by IPC in PC12 cells. (A) Compound C (Comp C) abolished IPC induced neuroprotection in PC12 cells. Cells were incubated with compound C 5 μM 60 min before the onset of IPC. Twelve hours after IPC, the cells were subjected to OGD for 10 h and cell viability was examined with CCK-8 kit. (B) Compound C reduced LC3II/LC3I ratio. The cells were incubated with compound C 5 μM 60 min before the onset of IPC. Then the cells were harvested 12 h after IPC and subjected to Western blot analysis. Bar represents mean ± SD, n = 3. *P < 0.05, ***P < 0.001 compared with the control group; $$$ P < 0.001 compared with the OGD group; %%% P < 0.001 compared with the IPC + OGD group; # P < 0.05 compared with the IPC group. |
|
| S7317 |
WZ4003WZ4003 is a highly specific NUAK kinase inhibitor with IC50 of 20 nM and 100 nM for NUAK1 and NUAK2 in cell-base assays, respectively, without significant inhibition on 139 other kinases. |
The AMPK inhibitor, WZ4003, and the p38 MAPK inhibitor, SB203580, could inhibit the APN-induced overexpression of CXCL1 and CXCL8 and h-JBMMSCs chemotaxis. After treated with WZ4003 and SB203580, the expression of CXCL1 (A and B) and CXCL8 (C and D) in the cells and supernatants of h-JBMMSCs treated with or without APN was evaluated by the ELISA assay (n = 3; *P < 0.05; **P < 0.01) |
|
| S7318 |
HTH-01-015HTH-01-015 is a potent and selective NUAK1 inhibitor with IC50 of 100 nM, >100-fold selectivity over NUAK2. |
Mouse BMDMs and human THP1 cells were treated with LPS (200 ng/ml) in the absence or presence of indicated AMPK activators (metformin, quercetin, resveratrol, AICAR, A-769662, and salicylate), AMPK inhibitors (compound C, WZ4003, and HTH-01-015), or HMGB1 inhibitor (glycyrrhizin) for 24 h. HMGB1 release in cell medium was assayed using ELISA kit, respectively (n = 3, *p < .05 versus LPS or Escherichia coli group).
|
|
| S7840 |
Dorsomorphin (Compound C)Dorsomorphin is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy. |
FGF21 activates myogenic and aerobic myofiber-associated genes expression via AMPK pathway. The activator (acadesine) or inhibitor (dorsomorphin) of AMPK pathway were used to treat the pcDNA3.1-21 or control transfected C2C12 myoblasts. For this experiment, four groups were set up: FGF21-ACA (pcDNA3.1-21‡acadesine), Control-ACA (control‡acadesine), FGF21-DOR (pcDNA3.1-21‡dorsomorphin), and Control-DOR(control‡dorsomorphin). The qRT-PCR was performed to detect the genes expression of FGF21 (A), AMPK (B), Sirt 1, Myoglobin(C), Desmin (D), MEF2c (E), a-actin (F). (G) The C2C12 myoblasts were transiently transfected with pCDNA3.1-21 or pCDNA3.1, Western blot showed FGF21 activated AMPK signal via FGF21-Sirt1-AMPK. For the phosphorylated AMPK (right), the intensity of band was normalized total AMPK, and then normalized by control. (H and I) FGF21, as well as AMPK activator acadesine (ACA), increased phosphorylation of AMPM, and myogenic genes expression, especially MyHC I, which was activated by ACA (FGF21‡ACA) and suppressed by AMPK inhibitor DOR(FGF21‡DOR). The data are presented as mean±SD (*P<0.05, **P<0.01, and P<0.001), n=ˆ3. |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1033 |
Nilotinib (AMN-107)Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition. |
Effect of nilotinib on Bcr-Abl kinase activity in ABCB1- and ABCG2- overexpressing CD34+CD38- cells. K562 parental cells and CD34+CD38- subpopulation isolated from K562 cells were treated with nilotinib at 0.01, 0.1 and 1.0 umol/L for 12 h. Equal amount of protein was loaded for western blot analysis as described in the Experimental section. The experiments were repeated at least three times independently, and a representative experiment is shown. |
|
| S2697 |
A-769662A-769662 is a potent, reversible AMPK activator with EC50 of 0.8 μM in cell-free assays, little effect on GPPase/FBPase activity. |
Cells were treated with CP, DOXO, SRT1720 (100 nM), EX527 (100 nM), A769662 (10 μM) and Compound C (1 μM) under normoxic or hypoxic conditions for 48 hours, and then their viabilities were measured by MTT. |
|
| S1802 |
AICAR (Acadesine)AICAR (Acadesine), an AMPK activator, results in accumulation of ZMP, which mimics the stimulating effect of AMP on AMPK and AMPK kinase. AICAR (Acadesine) induces mitophagy. Phase 3. |
Cultured hepatocytes were treated with 10 μM Compound C (Comp.C) for 30 min before treatment with 10 μM SAL, 1 mM AICAR for 3 h. Cell lysates were immunoblotted for the phosphorylation of AMPK, ACC, Akt and GSK3β. *P < 0.05, **P < 0.01 versus control; ##P < 0.01 versus SAL alone; †P < 0.05, ††P < 0.01 versus AICAR alone. Values are means ± SEM (n = 4). |
|
| S8953New |
ASP4132ASP4132 is a potent and orally active activator of Adenosine Monophosphate-Activated Protein Kinase (AMPK) with EC50 of 0.018 μM. ASP4132 is used as a clinical candidate for the treatment of human cancer. |
||
| S2542 |
Phenformin HClPhenformin HCl is a hydrochloride salt of phenformin that is an anti-diabetic drug from the biguanide class. It activates AMPK, increasing activity and phosphorylation. |
a set of RNAi-resistant rescue forms of Cdc37 plasmids were transfected into stable Cdc37-RNAi HCT116 cells. 24 h after transfection cells were treated with phenformin and then subjected to FLAG immunoprecipitation.
|
|
| S5284 |
Adenosine 5'-monophosphate monohydrateAdenosine 5'-monophosphate monohydrate (5'-AMP) is an activator of a class of protein kinases known as AMP-activated protein kinase (AMPK). |
||
| S8335 |
PF-06409577PF-06409577 is orally bioavailable AMPK activator with EC50 of 7 nM for α1β1γ1 in the TR-FRET assay and it shows no detectable inhibition of hERG in a patch-clamp assay (100 μM) and was not an inhibitor (IC50 > 100 μM) of the microsomal activities of major human cytochrome P450 isoforms. |
||
| S3832 |
EuphorbiasteroidEuphorbiasteroid, a component of Euphorbia lathyris L., inhibits adipogenesis of 3T3-L1 cells through activation of the AMPK pathway and induces HL-60 cells to apoptosis via promoting Bcl-2/Bax apoptotic signaling pathway in a dose-dependent manner. Euphorbiasteroid is a tricyclic diperpene of Euphorbia lathyris L., inhibits tyrosinase, and increases the phosphorylation of AMPK, with anti-cancer, anti-virus, anti-obesity and multidrug resistance-modulating effect. |
||
| S7898 |
GSK621GSK621 is a specific and potent AMPK activator. |
GSK621 dose-dependent activation of AMPK in erythroblasts. Western Blot analysis of PT172 AMPKα1, PS79 ACC and PS555 ULK1 in primary erythroblasts incubated for 3 h with increasing doses of GSK621. Anti-HSC70 was used as a loading control.
|
|
| S8654 |
ex229 (compound 991)EX229 (compound 991) is a potent AMPK activator that is 5-10-fold more potent than A769662 in activating AMPK. |
||
| S8803 |
MK-3903MK-3903 is a potent and selective AMPK activator with an EC50 of 8 nM for α1 β1 γ1 subunit. It activates 10 of the 12 pAMPK complexes with EC50 values in the range of 8-40 nM and maximal activation >50%. |
||
| S9096 |
ligustroflavoneLigustroflavone, isolated from the leaves of Turpinia montana, shows high antioxidant capacity and is reported to be an AMPK activator. |
||
| S7953 |
ETC-1002ETC-1002,also known as Bempedoic acid, is an orally available, once-daily LDL-C lowering small molecule designed to lower elevated levels of LDL-C and to avoid side effects associated with existing LDL-C lowering therapies.ETC-1002 is an activator of hepatic AMP-activated protein kinase (AMPK). It has potent inhibitory activity against hepatic ATP-citrate lyase(IC50=29 uM). |
||
| S4561 |
DanthronDanthron functions in regulating glucose and lipid metabolism by activating AMPK. Danthron is a natural product extracted from the traditional Chinese medicine rhubarb. Danthron used to be a laxativa and now is currently used as an antioxidant in synthetic lubricants, in the synthesis of experimental antitumor agents, as a fungicide and as an intermediate for making dyes. |
||
| S6221 |
Methyl cinnamateMethyl cinnamate, an active component of Zanthoxylum armatum, is a widely used natural flavor compound with antimicrobial and tyrosinase inhibitor activities. Methyl Cinnamate Inhibits Adipocyte Differentiation via Activation of the CaMKK2--AMPK Pathway in 3T3-L1 Preadipocytes. |
