AMPK Activator

Gypenoside A is an orally active triterpenoid compound that can be isolated from Gynostemma pentaphyllum. Gypenoside A has anti-inflammatory and antioxidant activities. Gypenoside A also has a certain protective effect on cardiomyocytes and can inhibit apoptosis. Gypenoside A can be used in the research of cardiovascular diseases and inflammation-related diseases.

Ginkgolide C is a flavone isolated from Ginkgo biloba leaves, possessing multiple biological functions, such as decreasing platelet aggregation and ameliorating Alzheimer disease.

Clitorin is an orally active flavonoid compound that can be isolated from Carica papaya. Clitorin is an inhibitor of EGFR (IC₅₀: 89.58 nM) and aromatase (IC₅₀: 77.41 nM). Clitorin has antioxidant and anti-tumor activities. In the DPPH and ABTS radical scavenging assays, Clitorin has IC₅₀ values of 91.96 ppm and 250.45 ppm, respectively. In addition, Clitorin can regulate lipogenesis and fatty acid oxidation and can be used in the research of non-alcoholic fatty liver disease.

p-Synephrine is an orally active alkaloid dietary supplement without indirect sympathomimetic activity or cardiovascular stimulatory activity. p-Synephrine stimulates AMPK phosphorylation and mediates Glut4 translocation to increase glucose consumption and lactate production in skeletal muscle cells. p-Synephrine also downregulates the p38 MAPK and NF-κB signaling pathways to inhibit pro-inflammatory cytokine production and alter oxidative metabolism. p-Synephrine exhibits low subchronic toxicity in mice. p-Synephrine can be applied to research related to systemic inflammatory response syndrome, obesity, and type 2 diabetes.

STF-118804 is a highly specific NAMPT inhibitor. STF-118804 activates AMPK and inhibits mTOR pathways. STF-118804 has antitumor activity against pancreatic cancer.

AMDE-1 is a potent autophagy inducer. AMDE-1 induces autophagy by the AMPK-mTORC1-ULK1 pathway and at the same time inhibited autophagy-mediated degradation by causing lysosome dysfunction. AMDE-1 can be used in research of cancer.

Fortunellin, is a flavonoid, that can be isolated from the fruits of Fortunella margarita (kumquat). Fortunellin exhibits little toxicity to mice and suppresses inflammation and ROS generation in H9C2 cells induced by LPS. Fortunellin protects against fructose-induced inflammation and oxidative stress by enhancing AMPK/Nrf2 pathway. Fortunellin can be used for diabetic cardiomyopathy research.

Jervine (11-Ketocyclopamine) is an orally active steroidal alkaloid and Hedgehog signaling pathway inhibitor. Jervine can be isolated from Veratrum californicum. Jervine regulates Wnt, inhibits the AKT/mTOR signaling pathway, and activates the AMPK signaling pathway. Jervine induces DNA damage, Apoptosis, Autophagy, ROS production and Mitochondrial damage. Jervine exhibits anti-cancer and anti-inflammatory activities. Jervine reduces tumor growth rate and weight in xenograft models. Jervine can be used in studies related to triple-negative breast cancer, nasopharyngeal carcinoma and non-small cell lung cancer.

Syringaresinol is a lignan-type phytochemical with anti-inflammatory activities. Syringaresinol inhibits the NF-κB and AKT signaling pathway in IL-1β-activated mouse chondrocytes. Syringaresinol increases phosphorylation of AMPK, eNOS, and intracellular Ca²⁺ levels in HUVECs. Syringaresinol attenuates osteoarthritis progression in mice with Destabilization of the Medial Meniscus (DMM)-induced osteoarthritis. Syringaresinol can be used for the study of osteoarthritis (OA).

PT1 is an AMPKα1 activator that directly activates the inactive truncated forms of AMPKα1 monomers.

Luteolin 7-diglucuronide is the major flavonoid isolated from Aloysia triphylla and Verbena officinalis.

Dimethoxycurcumin (DiMC) is a curcuminoid compound found in Curcuma longa. Dimethoxycurcumin is also an orally active thioredoxin reductase inhibitor (IC₅₀ = 5.4 μM) and androgen receptor antagonist. Dimethoxycurcumin inhibits thioredoxin reductase, leading to oxidized thioredoxin accumulation, ROS production, DNA damage, glutathione depletion, mitochondrial membrane potential decrease, ATP depletion, S phase arrest, and apoptosis. Dimethoxycurcumin inhibits NF-κB, NADPH oxidase subunits, ATP synthase subunits, CDK4, cyclin-D1, FASN, ACC, and the IRS2-PI3K-Akt pathway, while activating AMPK, ERK, and JNK. Dimethoxycurcumin can be used for research on cancer, arsenic-induced hepatotoxicity, and tuberculosis.

D-Arabinpyranose is is an orally active antidepressant and a growth inhibitor of C. elegans (IC₅₀ is 7.5 mM). D-Arabinpyranose can penetrate the blood-brain barrier, selectively interfere with the metabolism of D-ribose and D-fructose, and inhibit the growth of nematodes. D-Arabinpyranose can also inhibit the synthesis of cell biofilm and exert antibacterial activity. D-Arabinpyranose activates the ACSS2-PPARγ/TFEB-CRTC1 axis through the lysosomal AXIN-LKB1-AMPK pathway, inducing CRTC1 transcription, exerts antidepressant-like activity. D-Arabinpyranose is the ring-opened form of the aldopentose D-Arabinpyranose (HY-N7082).

8-Prenylnaringenin is an orally active prenyl flavonoid. 8-Prenylnaringenin can be isolated from the hop spike Humulus lupulus. 8-Prenylnaringenin activates the PI3K/Akt pathway and the AMPK pathway, upregulates OXPHOS complexes (II, III, and V) and Sirt1, and reduces ROS production and SOD activity. 8-Prenylnaringenin improves muscle atrophy and obesity and inhibits angiogenesis. 8-Prenylnaringenin exhibits anticancer activity against glioblastoma and colon cancer. 8-Prenylnaringenin also has LH/FSH regulatory activity. 8-prenylnaringenin may be used in bone health research.

RSVA405 is a potent, orally active activator of AMPK, with an EC₅₀ of 1 μM. RSVA405 facilitates CaMKKβ-dependent activation of AMPK, inhibits mTOR, and promotes autophagy to increase Aβ degradation. RSVA405 has anti-inflammatory effects through the inhibition of STAT3 function. RSVA405 can also be used for the research of obesity.

Biguanide is an orally active antihyperglycemic agent. Biguanide inhibits mitochondrial ATP production, activates the LKB1-AMPK signaling pathway, and damages the energy homeostasis. Biguanide enhances insulin-receptor activation and downstream signaling. Biguanide exhibits potential in ameliorating the type 2 diabetes and the insulin-associated cancers.

Lixumistat (IM156) hydrochloride is a potent and orally active AMPK activator and OXPHOS inhibitor. Lixumistat hydrochloride strongly activates AMPK, while it lacks the systemic metabolic regulatory effects of classic metformin, such as hypoglycemic and weight-lowering activities. Lixumistat hydrochloride exhibits significant therapeutic effects on cognitive decline associated with brain aging and pulmonary fibrosis.

Cimiracemoside C is an active component of Cimicifuga racemosa, activates AMPK, has the potential activity against diabetes.

KMS99220 is an orally active, blood-brain barrier-permeable activator of the Nrf2 inhibitory protein Keap-1. KMS99220 enhances the activity of AMPK, activates the Nrf2 signaling pathway, and reduces the phosphorylation of IκB, nuclear translocation of NFκB, as well as the phosphorylation levels of JNK, IKK and p38 MAPK via HO-1. KMS99220 binds to Keap1 to trigger the nuclear translocation of Nrf2, induces the expression of HO-1, NQO1, GCLC, GCLM and proteasome subunits; enhances proteasomal enzymatic activity; inhibits iNOS expression, nitric oxide production and IL-1β generation; attenuates microglial activation; reduces α-synuclein aggregation; and prevents dopaminergic neuron degeneration and motor dysfunction. KMS99220 prevents the degeneration of dopaminergic neurons in the substantia nigra, induces the expression of Nrf2 downstream target genes, and effectively ameliorates associated motor dysfunction in a mouse model of Parkinson's disease. KMS99220 is applicable to research related to Parkinson's disease.

IHMT-MST1-39 is an orally active inhibitor for MST kinase, with IC₅₀ of 42, 109, 286, 159 nM for MST1, MST2, MST3, MST4. IHMT-MST1-39 activates the AMPK signaling pathway in liver cells, reduces apoptosis of pancreatic β-cells. IHMT-MST1-39 can be used for the studies of type 1 diabetes (T1D) and type 2 diabetes (T2D).