CLP-290 is a novel and potent KCC2 modulator acting as a prodrug of CLP-257, and is highly selective for KCC2 over related Cl- transporters.

Physicochemical Properties

Molecular Formula	C19H21FN4O3S
Molecular Weight	404.4604
Exact Mass	404.131
CAS #	1181083-81-7
Related CAS #	1181083-81-7
PubChem CID	44188755
Appearance	Off-white to yellow solid powder
Density	1.5±0.1 g/cm3
Boiling Point	553.7±60.0 °C at 760 mmHg
Flash Point	288.6±32.9 °C
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.691
LogP	2.89
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	680
Defined Atom Stereocenter Count	0
SMILES	C1CCN(NC1)C2=NC(=O)/C(=C/C3=C(C=C(C=C3)F)OC(=O)N4CCCC4)/S2
InChi Key	DIXMMXNNKLCLOM-WJDWOHSUSA-N
InChi Code	InChI=1S/C19H21FN4O3S/c20-14-6-5-13(15(12-14)27-19(26)23-8-3-4-9-23)11-16-17(25)22-18(28-16)24-10-2-1-7-21-24/h5-6,11-12,21H,1-4,7-10H2/b16-11-
Chemical Name	[5-Fluoro-2-[(Z)-(2-hexahydropyridazin-1-yl-4-oxo-thiazol-5-ylidene)methyl]phenyl] pyrrolidine-1-carboxylate
Synonyms	CLP290 CLP 290 CLP-290
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vivo	In rats treated with morphine, CLP290 (oral gavage; 100 mg/kg; twice daily; 7 days) inhibits morphine-induced hyperalgesia in rats (MIH) and increases KCC2 activity and restores Cl- transport in superficial dorsal horn (SDH) neurons [1].
Animal Protocol	Animal/Disease Models: Adult male rat (300 g, >60 days after birth) [1] Doses: 100 mg/kg Route of Administration: po (oral gavage); 100 mg/kg; twice (two times) daily; 7 days Experimental Results: By restoring Cl - Transport or prevent defects in SDH, rescue established MIH and prevent its development.
References	[1]. Enhancing KCC2 function counteracts morphine-induced hyperalgesia. Sci Rep. 2017 Jun 20;7(1):3870. [2]. Chloride extrusion enhancers as novel therapeutics for neurological diseases. Nat Med. 2013 Nov;19(11):1524-8. [3]. Excitatory GABAergic Action and Increased Vasopressin Synthesis in Hypothalamic Magnocellular Neurosecretory Cells Underlie the High Plasma Level of Vasopressin in Diabetic Rats. Diabetes. 2018 Mar;67(3):486-495.

Solubility Data

Solubility (In Vitro)

DMSO : ~33.33 mg/mL (~82.41 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4724 mL	12.3622 mL	24.7243 mL
	5 mM	0.4945 mL	2.4724 mL	4.9449 mL
	10 mM	0.2472 mL	1.2362 mL	2.4724 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.