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CLP 257

Names

[ CAS No. ]:
1181081-71-9

[ Name ]:
CLP 257

[Synonym ]:
(5Z)-5-[(4-Fluoro-2-hydroxyphenyl)methylene]-2-(tetrahydro-1-(2H)-pyridazinyl)-4(5H)-thiazolone
(5Z)-5-(4-Fluoro-2-hydroxybenzylidene)-2-(tetrahydro-1(2H)-pyridazinyl)-1,3-thiazol-4(5H)-one
CLP257
MFCD28166488
4(5H)-Thiazolone, 5-[(4-fluoro-2-hydroxyphenyl)methylene]-2-(tetrahydro-1(2H)-pyridazinyl)-, (5Z)-

Biological Activity

[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.

[Related Catalog]:

Research Areas >> Neurological Disease
Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

[Target]

EC50: 616 nM (KCC2)[1]


[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].

[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.

[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.

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
473.3±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C14H14FN3O2S

[ Molecular Weight ]:
307.343

[ Flash Point ]:
240.0±31.5 °C

[ Exact Mass ]:
307.079071

[ LogP ]:
2.67

[ Vapour Pressure ]:
0.0±1.2 mmHg at 25°C

[ Index of Refraction ]:
1.697

[ Storage condition ]:
2-8°C

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Precautionary Statements ]:
P301 + P312 + P330

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

Related Compounds