Description
CLP257 is a selective K+-Cl− cotransporter KCC2 activator with an EC50 of 616 nM. CLP257 is inactive against NKCC1, GABAA receptors, KCC1, KCC3 or KCC4. CLP257 restores impaired Cl− transport in neurons with diminished KCC2 activity. CLP257 alleviates hypersensitivity in rats with neuropathic pain. CLP257 modulates plasmalemmal KCC2 protein turnover post-translationally.
Product information
CAS Number: 1181081-71-9
Molecular Weight: 307.34
Formula: C14H14FN3O2S
Chemical Name: (5Z)-2-(1,2-diazinan-1-yl)-5-[(4-fluoro-2-hydroxyphenyl)methylidene]-4,5-dihydro-1,3-thiazol-4-one
Smiles: OC1=CC(F)=CC=C1/C=C1\SC(=NC\1=O)N1CCCCN1
InChiKey: SKCADXVKQRCWTR-GHXNOFRVSA-N
InChi: InChI=1S/C14H14FN3O2S/c15-10-4-3-9(11(19)8-10)7-12-13(20)17-14(21-12)18-6-2-1-5-16-18/h3-4,7-8,16,19H,1-2,5-6H2/b12-7-
Technical Data
Appearance: Solid Power
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: DMSO : 17.86 mg/mL (58.11 mM; Need ultrasonic).
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined
HS Tariff Code: 382200
How to use
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.
In Vivo:
CLP257 (100 mg/kg; intraperitoneal injection; adult male rats) treatment induced a significant increase in mechanical sensitivity.
References:
- Gagnon M, et al. Chloride extrusion enhancers as novel therapeutics for neurological diseases. Nat Med. 2013 Nov;19(11):1524-8.
- Ferrini F, et al. Enhancing KCC2 function counteracts morphine-induced hyperalgesia. Sci Rep. 2017 Jun 20;7(1):3870.
Products are for research use only. Not for human use.
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