| Identification | Back Directory | [Name]
SC-396658 | [CAS]
924416-43-3 | [Synonyms]
104890
CS-918
AdipoRon
AdipiRon
SC-396658
AdipoR agonist
AdipoRon (SC-396658)
924416-43-3, CFCD924416433,
2-(4-benzoylphenoxy)-N-(1-benzylpiperidin-4-yl)acetaMide
2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]acetamide
ACETAMIDE, 2-(4-BENZOYLPHENOXY)-N-[1-(PHENYLMETHYL)-4-PIPERIDINYL]-
2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]acetamide AdipoRon | [Molecular Formula]
C27H28N2O3 | [MDL Number]
MFCD08271060 | [MOL File]
924416-43-3.mol | [Molecular Weight]
428.523 |
| Chemical Properties | Back Directory | [Melting point ]
106-108°C | [Boiling point ]
645.3±55.0 °C(Predicted) | [density ]
1.21±0.1 g/cm3(Predicted) | [storage temp. ]
room temp | [solubility ]
DMSO: soluble10mg/mL, clear | [form ]
powder | [pka]
13.92±0.20(Predicted) | [color ]
white to beige | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months. | [InChI]
InChI=1S/C27H28N2O3/c30-26(28-24-15-17-29(18-16-24)19-21-7-3-1-4-8-21)20-32-25-13-11-23(12-14-25)27(31)22-9-5-2-6-10-22/h1-14,24H,15-20H2,(H,28,30) | [InChIKey]
SHHUPGSHGSNPDB-UHFFFAOYSA-N | [SMILES]
C(NC1CCN(CC2=CC=CC=C2)CC1)(=O)COC1=CC=C(C(=O)C2=CC=CC=C2)C=C1 |
| Hazard Information | Back Directory | [Description]
Adiponectin expressed by adipocytes exerts antidiabetic effects by binding to adiponectin receptor (AdipoR)1, which activates AMPK pathways, and AdipoR2, which activates PPARα pathways. AdipoRon is an orally active small molecule AdipoR agonist that binds AdipoR1 and AdipoR2 with KD values of 1.8 and 3.1 μM, respectively.1 At 50 mg/kg, it acts similarly to adiponectin, activating AMPK and PPARα pathways and reducing insulin resistance and glucose intolerance in wild type mice fed a high-fat diet and in genetically obese db/db mice.1 | [Uses]
AdipoR agonist that binds to both AdipoR1 and AdipoR2. | [Biochem/physiol Actions]
AdipoRon is an adiponectin agonist that binds to and activates adiponectin receptors AdipoR1 and AdipoR2, activating AMPK and PPAR-α pathways, and ameliorating insulin resistance and glucose intolerance in mice fed a high-fat diet in a manner similar to adiponectin itself. AdipoRon did not affect body weight, but did increase the expression of genes involved in fatty-acid oxidation, decreased tissue triglyceride content, and prolonged the shortened lifespan of db/db mice. | [Enzyme inhibitor]
This orally bioavailable adiponectin receptor agonist (FW = 428.52 g/mol;
CAS 924416-43-3; Solubility: 100 mg/mL DMSO; <1 mg/mL H2O), also
known as 2- (4-benzoylphenoxy) -N- (1-benzylpiperidin-4-yl) acetamide,
stimulates AMPK-mediated phosphorylation and activation of AdipoR1
(Kd = 1.8 μM) and AdipoR1 (Kd = 3.1 μM), which are orientated oppositely
to most GPCRs within the membrane (i.e., cytoplasmic N-terminus,
extracellular C-terminus), such that they cannot associate with G-proteins.
In wild type mice, AdipoRon (orally administered at 50?mg/kg) improves
insulin resistance, glucose intolerance, and dyslipidemia by activating
AdipoR1–AMPK–PGC-1α pathways in skeletal muscle, while by
activating AdipoR2–PPAR-α (Peroxisome Proliferator-Activated Receptor)
pathways in the liver. | [in vivo]
AdipoRon (50?mg/kg, i.v.) cuases significant phosphorylation of AMPK in skeletal muscle and liver of wild-type mice but not Adipor1?/??Adipor2?/? double-knockout mice[1]. AdipoRon (0.02, 0.1, and 0.5 mg/kg, i.g.) alleviates D-GalN induced hepatotoxicity in mice, and prevents hepatic architecture distortion against D-GalN challenge. The hepatoprotective potential of AdipoRon is particularly evident in higher dosages (0.1 and 0.5 mg/kg)[2]. Enhanced cardiomyocyte apoptosis in APN-deficient mice is rescued by AdipoRon (50 mg/kg, p.o.) administration. Antiapoptotic effect of AdipoRon is attenuated but not lost in AMPK-DN mice[3]. | [storage]
+4°C | [Clinical claims and research]
AdipoRon is a small, synthetic molecule that binds both adiponectin receptors AdipoR1 and AdipoR2 with a Kd of approximately 1.8 and 3.1 mM, respectively. This synthetic adiponectin receptor agonist exhibits strong anti-obesity, anti-diabetic, anti-depressant, anti-ischemic, and anti-hypertrophic activities. AdipoRon behaves similarly to adiponectin in muscle and liver tissues of mice that are fed a high-fat diet, reducing insulin resistance and glucose intolerance through activation of the AMPK and PPAR-α pathways. Clinically, AdipoRon can be used to improve post-traumatic stress disorder, anxiety, and systemic sclerosis; it is being evaluated for the treatment of several forms of cancer, including pancreatic ductal adenocarcinoma, myeloma, breast, and ovarian cancer. Treatment of myeloma cell lines with AdipoRon significantly induced expression of the apoptosis-related proteins cleaved caspase-3 and cleaved PARP, and inhibited cell proliferation. A study using a mouse model of hypertension indicated that this AdipoRon treatment could prevent renal fibrosis in hypertensive patients. | [References]
1) Okada-Iwabu?et al. (2013),?A small-molecule AdipoR agonist for type 2 diabetes and short life obesity; Nature 503?493
2) Fairaq?et al.?(2017),?AdipoRon, an adiponectin receptor agonist, attenuates PDGF-induced VSMC proliferation through inhibition of mTOR signaling independent of AMPK: Implications toward suppression of neointimal hyperplasia; Pharmacol. Res.?119?289 |
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| Company Name: |
LETOPHARM LIMITED
|
| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
| Company Name: |
Sigma-Aldrich
|
| Telephone: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
|