| Description | CLP257 is a selective K+-Cl− cotransporter KCC2 activator (EC50: 616 nM) and it is inactive against NKCC1, GABAA receptors, KCC1, KCC3 or KCC4. CLP257 alleviates hypersensitivity in rats with neuropathic painc and it also modulates plasmalemmal KCC2 protein turnover post-translationally. CLP257 restores impaired Cl− transport in neurons with diminished KCC2 activity. |
| In vitro | Oocyte pre-incubation with CLP257 (200 nM) increases KCC2 transport activity by 61%. However, it causes no change in other CCCs. There is no change in [Cl?]i in HEK293-cl cells when incubated with CLP257. CLP257 (50 μM) provokes < 0.2% of the effect of 5 μM muscimol in CHO cells transduced with recombinant α1β2γ2 GABAA receptors. Dose-dependent antagonism is also observed between CLP257 and the recently characterized KCC2 antagonist VU024055119 [1]. |
| In vivo | CLP257 (100?mg/kg; i.p.; adult male rats) treatment causes an obvious increase in mechanical sensitivity [2]. |
| Target activity | KCC2:（EC50）616 nM |
| molecular weight | 307.34 |
| Molecular formula | C14H14FN3O2S |
| CAS | 1181081-71-9 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 17.86 mg/mL (58.11 mM), Sonication is recommended. |
| References | 1. Gagnon M, et al. Chloride extrusion enhancers as novel therapeutics for neurological diseases. Nat Med. 2013 Nov;19(11):1524-8. 2. Ferrini F, et al. Enhancing KCC2 function counteracts morphine-induced hyperalgesia. Sci Rep. 2017 Jun 20;7(1):3870. |