1181081-71-9

1181081-71-9 structure

Name: CLP 257
Chemical Name: CLP257
CAS Number: 1181081-71-9
Molecular Formula: C₁₄H₁₄FN₃O₂S
Molecular Weight: 307.343
Catalog: Signaling Pathways Membrane Transporter/Ion Channel Potassium Channel
Create Date: 2020-01-19 21:17:00
Modify Date: 2024-08-09 11:12:10
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.

Name	CLP257
Synonyms	(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)-

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.

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

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H302
Precautionary Statements	P301 + P312 + P330
Hazard Codes	Xi
RIDADR	NONH for all modes of transport

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