| Description |
CLP257 (CLP-257) is a potent, selective K+-Cl- cotransporter KCC2 activator with EC50 of 616 nM; displays selectivity for KCC2 over other KCC family members, NKCC1 and GABAA receptors, and a panel of 55 other receptors; restores impaired Cl(-) transport in neurons, rescues KCC2 plasma membrane expression; renormalizes stimulus-evoked responses in spinal nociceptive pathways in a rat model of neuropathic pain.
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| Related Catalog |
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| Target |
EC50: 616 nM (KCC2)[1]
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| In Vitro |
There is no change in [Cl−]i in HEK293-cl cells when incubated with CLP257, indicating inactivity on NKCC1, KCC1, KCC3 or KCC4. Oocyte pre-incubation with CLP257 (200 nM) increases KCC2 transport activity by 61%, but causes no change in other CCCs. Functional, dose-dependent antagonism is also observed between CLP257 and the recently characterized KCC2 antagonist VU024055119. CLP257 (50 μM) provokes < 0.2% of the effect of 5 μM muscimol in CHO cells transduced with recombinant α1β2γ2 GABAA receptors, indicating negligible agonist activity of CLP257 on GABAA receptors[1].
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| In Vivo |
CLP257 (100 mg/kg; intraperitoneal injection; adult male rats) treatment induced a significant increase in mechanical sensitivity[2]. Animal Model: Adult male rats (300 g) injected with Morphine[2] Dosage: 100 mg/kg Administration: Intraperitoneal injection Result: Induced a significant increase in mechanical sensitivity.
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| 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.
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