GLUT4 Activator

Rhoifolin is a flavone glycoside can be isolated from Rhus succedanea. Rhoifolin has anti-diabetic effect acting through enhanced adiponectin secretion, tyrosine phosphorylation of insulin receptor-β and glucose transporter 4 (GLUT 4) translocation. Rhoifolin has an anti-inflammatory action via multi-level regulation of inflammatory mediators. Rhoifolin ameliorates titanium particle-stimulated osteolysis and attenuates osteoclastogenesis via RANKL-induced NF-κB and MAPK pathways. Rhoifolin also has cytotoxic activity against different cancer cell lines.

MOTS-c (human) is a blood-brain barrier-penetrating, mitochondrial-derived peptide that modulates the AMPK/PGC-1α pathway to enhance insulin sensitivity. MOTS-c (human) inhibits the folate cycle and de novo purine synthesis, increases AICAR levels to activate AMPK, and then regulates the Nrf2/Keap1 antioxidant pathway and inhibits the NF-κB inflammatory pathway, while promoting mitochondrial biogenesis and energy metabolism. MOTS-c (human) has the effects of improving glucose and lipid metabolism, anti-oxidative stress, anti-inflammatory and neuroprotection, and can be used in the study of type 2 diabetes, traumatic brain injury, inflammatory diseases and aging-related metabolic disorders.

MOTS-c (human) acetate is a blood-brain barrier-penetrating, mitochondrial-derived peptide that modulates the AMPK/PGC-1α pathway to enhance insulin sensitivity. MOTS-c (human) acetate inhibits the folate cycle and de novo purine synthesis, increases AICAR levels to activate AMPK, and then regulates the Nrf2/Keap1 antioxidant pathway and inhibits the NF-κB inflammatory pathway, while promoting mitochondrial biogenesis and energy metabolism. MOTS-c (human) acetate has the effects of improving glucose and lipid metabolism, anti-oxidative stress, anti-inflammatory and neuroprotection, and can be used in the study of type 2 diabetes, traumatic brain injury, inflammatory diseases and aging-related metabolic disorders.

Antidiabetic agent 9 is an orally active antidiabetic agent. Antidiabetic agent 9 promotes the translocation of GLUT4 to the cell surface, activates the AMPK signaling pathway, and has no effect on the PI-3-K/AKT signaling pathway. Antidiabetic agent 9 reduces blood glucose levels in Streptozotocin (HY-13753)-induced diabetic rats. Antidiabetic agent 9 can be used in the research of diabetes.

D927 (DS11252927) is an orally active glucose transporter type 4 (GLUT4) translocation activator with an EC₅₀ of 0.14 μM. D927 enhances the binding affinity of PI3Kα catalytic subunit p110α to canonical RAS proteins (KRAS4A, KRAS4B) and RRAS, RRAS2, MRAS. D927 activates the PI3Kα-AKT pathway (increasing phosphorylation of AKT, p70S6 kinase) without affecting the RAF-ERK1/2 pathway. D927 improves hyperglycemia in type 1 and type 2 diabetes mice model. D927 can be used for the study of glucose homeostasis disorders and diabetes.

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.

Licarin B, a nitric oxide production inhibitor extracted from the component of the seeds of Myristica fragrans, improves insulin sensitivity via PPARγ and activation of GLUT4 in the IRS-1/PI3K/AKT pathway.

DS02312223 (D223) is a molecular glue that promotes the binding of RAS to PI3Kα, with a K_d of 0.76 μM for p110α. DS02312223 increases the binding affinity between GTP-bound KRAS (KRAS-GMPPNP) and p110α by nearly three orders of magnitude (K_D = 0.017 μM). DS02312223 stimulates the translocation of GLUT4 to the plasma membrane. DS02312223 promotes glucose uptake in the absence of insulin. DS02312223 can be used in diabetes research.

Deoxyandrographolide is an orally active lactone found in the Andrographis paniculata Nees. Deoxyandrographolide shows a K_D of 38.4 μM of HDAC1. Deoxyandrographolide enhances GLUT4 plasma membrane translocation, activates PI3K and AMPK-dependent signaling pathways, suppresses fasting blood glucose, serum insulin, triglycerides, and LDL-cholesterol levels. Deoxyandrographolide enhances HDAC1 expression via inhibited ubiquitination degradation, represses H3K4me3, improves chromosome stability, and restrains aging biomarkers p16, p21, γH2A.X, p53 and ROS production. Deoxyandrographolide interacts with Foot-and-Mouth Disease Virus 3Cpro active site, inhibits protease and IFN-antagonist activity, derepresses ISG expression, and inhibits viral replication. Deoxyandrographolide can be used for the researches of type 2 diabetes mellitus, vascular senescence and virus infection.

Sennidin B, a stereoisomer isolated from the leaves of Cassia angustifolia, has lower activity than Sennidin A. Sennidin A inhibits HCV NS3 helicase, with an IC₅₀ of 0.8 μM. Sennidin A induces phosphorylation of Akt and glucose transporter 4 (GLUT4) translocation. Sennidin A stimulates the glucose incorporation .

Pterosin A ((2S)-Pterosin A) is a sesquiterpene compound. Pterosin A is an orally active AMPK activator with anti-diabetic effect. Pterosin A can promote glucose uptake, increase serum insulin, and improve hyperglycemia and glucose intolerance. Pterosin A can prevent insulin-secreting cells death and reduce ROS production. Pterosin A can be used for the research of metabolic disease, such as diabetes.

DS-1150b is an orally active GLUT4 activator. DS-1150b has the activity of activating GLUT4 transport and can promote the translocation of GLUT4 to the cell membrane in skeletal muscle cells. DS-1150b has shown hypoglycemic effects in the Zucker obese rat model and can be used in the study of type 2 diabetes mellitus (T2DM).

Chiisanogenin is an orally active triterpenoid. Chiisanogenin reduces postprandial blood glucose by promoting GLUT4 translocation and glucose uptake via activation of the IRS-1/PI3K/Akt signaling pathway. Chiisanogenin binds to MLKL and inhibits its phosphorylation and oligomerization, maintains lysosomal integrity, restores autophagic flux, and suppresses NLRP3 inflammasome activation and pyroptosis. Chiisanogenin inhibits xanthine oxidase activity and regulates oxidative stress and ion pump activity. Chiisanogenin binds to or inhibits PKA, H⁺/K⁺-ATPase and β-glucuronidase. Chiisanogenin possesses multiple pharmacological activities, including broad-spectrum antibacterial activity, anticancer, anti-inflammatory, antirheumatic, renoprotective, cardioprotective and antiarrhythmic effects. Chiisanogenin can be used in research related to type 2 diabetes, rheumatoid arthritis, myocardial injury, hepatocellular carcinoma and ventricular arrhythmia^.

Antidiabetic agent 7 (Compound 5m) is hyperglycemic inhibitor. Antidiabetic agent 7 exhibits promising potency to stimulate GLUT4 translocation in skeletal muscle cells via activating AMPK-dependent pathway. Antidiabetic agent 7 reduces blood glucose levels. Antidiabetic agent 7 shows favorable pharmacokinetic properties. Antidiabetic agent 7 is potential to be used for anti-hyperglycemic research.

Sennidin A, isolated from the leaves of Cassia angustifolia, inhibits HCV NS3 helicase, with an IC₅₀ of 0.8 μM. Sennidin A induces phosphorylation of Akt and glucose transporter 4 (GLUT4) translocation. Sennidin A stimulates the glucose incorporation.