JNJ-26489112 

JNJ-26489112, a CNS-active agent, exhibits broad-spectrum anticonvulsant activity in rodents against audiogenic, electrically-induced, and chemically-induced seizures. JNJ-26489112 inhibits voltage-gated Na⁺ channels and N-type Ca²⁺ channels, and is effective as a K⁺ channel opener. JNJ-26489112 has very weak inhibition of CA-II (IC₅₀=35 μM) and CA-I (18 μM)^[1].

JNJ-26489112 inhibits calcium influx in response to depolarization (fluorescence-based assay) with an IC₅₀ of 34 μM. In a whole-cell, patch-clamp experiment with low-frequency stimulation (0.07 Hz), intended to measure N-type channel activity directly, JNJ-26489112 causes a concentration-dependent increase in inhibition, with an IC₅₀ of 70 μM. JNJ-26489112 is a KCNQ2 channel opener, particularly at -50 mV^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

JNJ-26489112 (i.p.) effectively blocks chemically-induced, forelimb clonic seizures in mice ( male CF-1 albino mice) that are caused by subcutaneous bicuculine (Bic), picrotoxin (Pic), or pentylenetetrazol (PTZ), with 1-h ED50 values of 197, 189, or 109 mg/kg, respectively^[1].
In adult male rats, JNJ-26489112 (p.o; 10 mg/kg) treatment shows the Cmax, tmax, F, t1/2, and AUC (total exposure) values in plasma were 9090 ng/mL (33 μM), 53 min, 95%, 8.2 h, and 53,200 ng-h/mL. Linear, dose-related increases in exposure were observed at 10, 30, and 300 mg/kg. JNJ-26489112 (i.v.; 2 mg/kg) treatment shows the Vdss is 390 mL/kg and the CL is 96 mL/h-kg. In female beagle dogs, JNJ-26489112 (p.o; 10 mg/kg) treatment shows the Cmax, tmax, F, t1/2, and AUC values in plasma are 11,500 ng/mL (41 μM), 55 min, 83%, 20 h, and 212,000 ng-h/mL. . JNJ-26489112 (i.v.; 2 mg/kg) treatment shows the the Vdss and CL values are 630 mL/kg and 30 mL/h-kg, respectively^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

278.71

C₉H₁₁ClN₂O₄S

871824-55-4

Solid

White to light yellow

O=S(N)(NC[C@@H]1OC2=CC=C(Cl)C=C2OC1)=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. McComsey DF, et al. Novel, broad-spectrum anticonvulsants containing a sulfamide group: pharmacological properties of (S)-N-[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112). J Med Chem. 2013;56(22):9019-9030.  [Content Brief]