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Chemical Structure| 1261289-04-6 Chemical Structure| 1261289-04-6

Structure of O-304
CAS No.: 1261289-04-6

Chemical Structure| 1261289-04-6

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O-304 is a first-in-class, orally available pan-AMPK activator, which increases AMPK activity by suppressing the dephosphorylation of pAMPK. O-304 exhibits a great potential as a drug to treat type 2 diabetes (T2D) and associated cardiovascular complications [1][2].

Synonyms: O-304X

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Product Details of O-304

CAS No. :1261289-04-6
Formula : C16H11Cl2N3O2S
M.W : 380.25
SMILES Code : ClC1=CC=C(C=C1)CN2C(N=C(NC(C3=CC=C(Cl)C=C3)=O)S2)=O
Synonyms :
O-304X
MDL No. :MFCD31657425
InChI Key :WEDWLYRQKUTOAX-UHFFFAOYSA-N
Pubchem ID :50923806

Safety of O-304

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Related Pathways of O-304

epigenetics
PI3K-AKT

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
hepatocytes 2.5 μM, 5 μM, 10 μM O304 dose-dependently suppressed lipid synthesis PMC6124394
mouse primary islets 2.5 μM, 5 μM, 10 μM O304 increased p-T172 AMPK levels PMC6124394
INS-1 insulinoma cells 2.5 μM, 5 μM, 10 μM O304 increased p-T172 AMPK levels PMC6124394
Human skeletal myotubes 2.5 μM, 5 μM, 10 μM O304 increased 2-DeoxyD-glucose (2-DG) uptake in a dose- and AMPK-dependent manner in the absence of insulin PMC6124394
Wi-38 human lung fibroblast cells 2.5 μM, 5 μM, 10 μM O304 increased pAMPK, pACC, and ATP/protein ratio in a dose-dependent manner PMC6124394
INS-1E cells 5 μM 4 days or 2 h To evaluate the effect of O304 on insulin secretion under hyperglycemic conditions, results showed that O304 prevented and partly reversed the negative effects of chronic hyperglycemia on glucose-stimulated insulin secretion (GSIS). PMC10457357
C2C12 myotubes 0.625, 1.25, 2.5 μM 4 h To assess the uncoupling potential of O304, results showed that O304 dose-dependently increased oxygen consumption rate (OCR), indicating its function as a mitochondrial uncoupler. PMC10457357
mouse hippocampal neurons 50 nM 1 h Pre-treatment with O304 abrogated the suppression effect of NTRK1 knockdown on the activity of the AMPK/ULK1/FUNDC1 pathway and reversed the inhibitory effect of NTRK1 knockdown on mitophagy. PMC10618268
Human aortic smooth muscle cells 50 nM 48 h O304 activated AMPK signaling and prevented VSMC phenotypic switching from the contractile to the synthetic phenotype. PMC11637863
CBA x C57Bl/6 F1 hybrid mouse islets 5 μM 96 h O304 significantly reduced Aldh1a3 expression under high glucose conditions, alleviating β-cell stress PMC8702551

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Diet-induced obese (DIO) mice Oral gavage 100 mg/kg Once daily for 8 weeks O304 and O304+Metformin significantly reduced fasted glucose and plasma insulin levels and prevented insulin resistance PMC6124394
Mice STZ-induced diabetic mice and db/db mice Formulated in diet 0.25, 0.5, 1.0 mg/g Continuous treatment To assess the ameliorative effects of O304 on hyperglycemia and its protective effects on β-cell function. Results showed that O304 significantly improved hyperglycemia by dually promoting muscle glucose effectiveness and preserving β-cell function. PMC10457357
ApoE-deficient male mice Abdominal aortic aneurysm model Oral 200 mg/kg Once every 3 days for 28 days O304 significantly activated AMPK signaling, increased the proportion of contractile VSMCs, and reduced AAA formation and blood pressure. PMC11637863
Mice Aged mouse model Oral 0.25 or 0.5 mg/g Continued for 12 months O304 prevented and reverted age-associated hyperinsulinemia and insulin resistance, and improved cardiac function and exercise capacity in aged mice. PMC8602430
CBA mice High-fat diet-induced obesity and diabetes model Oral 0.8 mg/g Continuous for 9 weeks O304 treatment significantly improved glucose homeostasis, reduced fasting blood glucose and insulin levels, alleviated β-cell stress, and restored islet gene expression profiles PMC8702551

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.63mL

0.53mL

0.26mL

13.15mL

2.63mL

1.31mL

26.30mL

5.26mL

2.63mL

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