An antiepileptic compound
Stiripentol is an LDH inhibitor. It is a new-generation antiepileptic drug, and its chemical structure is unrelated to other antiepileptic drugs. Seizures and epileptiform activity are reduced by inhibition of the metabolic pathway via lactate dehydrogenase (LDH), which is a component of the astrocyte-neuron lactate shuttle [1].
Stiripentol is used for the treatment of Dravet syndrome, a rare form of epilepsy (26). Stiripentol (300 mg/kg ip) had a small effect on high-voltage spikes in the kainate model. Stiripentol (500 mM) inhibited the lactate-to-pyruvate conversion as well as the pyruvate-to-lactate conversion by both human LDHs. Lineweaver-Burk plots revealed that the inhibition by stiripentol was noncompetitive, suggesting that stiripentol binds to the LDHs at a different site with lactate and pyruvate. [1]
参考文献:
[1]. Sada N, Lee S2, Katsu T et al. Epilepsy treatment. Targeting LDH enzymes with a stiripentol analog to treat epilepsy. Science. 2015 Mar 20;347(6228):1362-7.
| Kinase experiment [1]: | |
|
Target |
purified mammalian LDH1 and LDH5 |
|
Preparation method |
The solubility of this compound in DMSO is >9.9mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
500 uM |
|
Applications |
Stiripentol inhibited the lactate-to-pyruvate conversion and pyruvate-to-lactate conversion by two human LDHs (LDH1 and LDH5). The inhibition by stiripentol was noncompetitive, suggesting that stiripentol binds to the LDHs at a different site with lactate and pyruvate. |
| Animal experiment [1]: | |
|
Animal models |
kainate mice model |
|
Dosage form |
300 mg/kg ip |
|
Application |
In mice after the kainate injection, stiripentol (300 mg/kg ip) had a small effect on high-voltage spikes. Stiripentol-like compound isosafrole (200 to 300 mg/kg ip) strongly suppressed spontaneous high-voltage spikes and paroxysmal discharges. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
参考文献: [1]. Sada N, Lee S2, Katsu T et al. Epilepsy treatment. Targeting LDH enzymes with a stiripentol analog to treat epilepsy. Science. 2015 Mar 20;347(6228):1362-7. | |
动态评分
0.0