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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
mouse primary islets mouse primary islets O304 increased p-T172 AMPK levels JCI Insight. 2018 Jun 21;3(12):e99114.
INS-1 insulinoma cells INS-1 insulinoma cells O304 increased p-T172 AMPK levels JCI Insight. 2018 Jun 21;3(12):e99114.
hepatocytes hepatocytes O304 dose-dependently suppressed lipid synthesis JCI Insight. 2018 Jun 21;3(12):e99114.
Human skeletal myotubes Human skeletal myotubes O304 increased 2-DeoxyD-glucose (2-DG) uptake in a dose- and AMPK-dependent manner in the absence of insulin JCI Insight. 2018 Jun 21;3(12):e99114.
Wi-38 human lung fibroblast cells Wi-38 human lung fibroblast cells O304 increased pAMPK, pACC, and ATP/protein ratio in a dose-dependent manner JCI Insight. 2018 Jun 21;3(12):e99114.
INS-1E cells INS-1E cells 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). Commun Biol. 2023 Aug 25;6(1):877.
C2C12 myotubes C2C12 myotubes 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. Commun Biol. 2023 Aug 25;6(1):877.
mouse hippocampal neurons mouse hippocampal neurons 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. Cell Death Discov. 2023 Oct 31;9(1):404.
Human aortic smooth muscle cells Human aortic smooth muscle cells O304 activated AMPK signaling and prevented VSMC phenotypic switching from the contractile to the synthetic phenotype. Front Pharmacol. 2024 Nov 29;15:1457817.
CBA x C57Bl/6 F1 hybrid mouse islets CBA x C57Bl/6 F1 hybrid mouse islets O304 significantly reduced Aldh1a3 expression under high glucose conditions, alleviating β-cell stress Sci Rep. 2021 Dec 23;11(1):24410.

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 JCI Insight. 2018 Jun 21;3(12):e99114.
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. Commun Biol. 2023 Aug 25;6(1):877.
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. Front Pharmacol. 2024 Nov 29;15:1457817.
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. Commun Biol. 2021 Nov 18;4(1):1306
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 Sci Rep. 2021 Dec 23;11(1):24410.

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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