| Identification | Back Directory | [Name]
PS10 | [CAS]
1564265-82-2 | [Synonyms]
PS10
PS10,PS-10
2-[(24-Dihydroxyphenyl)sulfonyl]-23-dihydro-1H-isoindole-46-diol
1H-Isoindole-4,6-diol, 2-[(2,4-dihydroxyphenyl)sulfonyl]-2,3-dihydro- | [Molecular Formula]
C14H13NO6S | [MDL Number]
MFCD31814433 | [MOL File]
1564265-82-2.mol | [Molecular Weight]
323.32 |
| Chemical Properties | Back Directory | [Boiling point ]
661.7±65.0 °C(Predicted) | [density ]
1.696±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: 2mg/mL, clear | [form ]
Solid | [pka]
7.05±0.35(Predicted) | [color ]
Light yellow to khaki |
| Hazard Information | Back Directory | [Biological Activity]
2-[(2,4-dihydroxyphenyl) sulfonyl]isoindoline-4,6-diol (PS10) can be considered as a therapeutic method to preserve glucose and lipid homeostasis in obesity and type 2 diabetes (T2D). It can induce pyruvate dehydrogenase complex (PDC) activity in liver and kidney. It is also considered as an effective PDK inhibitor to tre at diabetic cardiomyopathy. In the normal myocardiumPS10 helps to enhance fractional carbohydrate oxidation.''PS10 is a potent and selective PDK (Pyruvate dehydrogenase kinase) inhibitor th at improves glucose tolerance and lessens hepatic steatosis in diet-induced obese mice. PS10 binds to the ATP-binding pocket of PDKs. | [Enzyme inhibitor]
This novel ATP binding pocket-directed inhibitor (FW = 323.32 g/mol), systematically named 2-[(2,4-dihydroxyphenyl)sulfonyl]isoindoline-4,6- diol, targets all four PDK isoforms, with an IC50 = 0.8 μM and Ki = 0.24 μM for PDK2. Its design is based on structure-guided design, converting a known Hsp90 inhibitor into a series of highly specific PDK inhibitors, substituting a sulfonyl group in place of a carbonyl in the parent compound. This modification results in weak binding to Hsp90 (Ki = 47 μM). PS10 administration (70 mg/kg) to diet-induced obese mice significantly augments PDC activity with reduced phosphorylation in different tissues. Prolonged treatment improves glucose tolerance, with notably lessened hepatic steatosis in a mouse model. Such findings suggest pharmacological targeting of PDK may be useful in controlling glucose and fat levels in obesity and type 2 diabetes. |
|
| Company Name: |
Merck KGaA
|
| Tel: |
(+86) 21 2033 8288 |
| Website: |
http://www.sigmaaldrich.cn |
|