1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEML335Cat. No.: HY-104005CAS No.: 825658-06-8分式: CHClNOS分量: 373.25作靶點: Potassium Channel作通路: Membrane Transporter/Ion Channel儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 155 mg/mL (415.27

2、 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.6792 mL 13.3958 mL 26.7917 mL5 mM 0.5358 mL 2.6792 mL 5.3583 mL10 mM 0.2679 mL 1.3396 mL 2.6792 mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 ML335是TREK-1 和 TREK-2 的選擇性激活劑。IC50 & Target TREK-

3、1, TREK-2體外研究Xenopus oocyte two-electrode voltage-clamp measurements show that ML335 and ML402 activate K2P2.1and K2P10.1 but not K2P4.1 (14.32.7M, K2P2.1-ML335; 13.77.0M, K2P2.1-ML402; 5.20.5M,K2P10.1-ML335; and 5.91.6M, K2P10.1-ML402). Swapping the Lys271 equivalent between K2P2.1 and1/2 Master of

4、 Small Molecules 您邊的抑制劑師www.MedChemEK2P4.1 results in a clear phenotype reversal for ML335 and M402 activation. ML335 and ML402 activateK2P2.1 in HEK293 cells similar to their effects in Xenopus oocytes (5.20.8M and 5.91.6M for ML335and ML402, respectively (n3) 1.PROTOCOLCell Assay 1 Mouse K2P2.1, h

5、uman K2P4.1, and mutants are expressed from a previously described pIRES2-EGFPvector in HEK293T cells (ATTC). 70% confluent cells are transfected (in 35-mm diameter wells) withLipofectAMINE 2000 for 6h, and plated onto coverslips coated with Matrigel. Effects of ML335, ML402 andarachidonic acid on K

6、2P2.1 current at 0mV are measured by whole-cell patch-clamp experiments 24h aftertransfection. Acquisition and analysis are performed using pCLAMP9 and an Axopatch 200B amplifier.Pipette resistance ranges from 1 to 1.5M. Pipette solution contains the following: 145mM KCl, 3mMMgCl2, 5mM EGTA and 20mM

7、 HEPES (pH 7.2 with KOH). Bath solution contains the following: 145mMNaCl, 5mM KCl, 1mM CaCl2, 3mM MgCl2 and 20mM HEPES (pH 7.4 with NaOH). K2P2.1 currents areelicited by a 1s ramp from -100 to +50mV from a -80mV holding potential. After stabilization of the basalcurrent, ML335 and ML402 are perfuse

8、d at 200mL per hour until potentiation is stably reached 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Lolicato M, et al. K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site. Nature. 2017 Jul 20;547(7663):364-368.McePdfHeightCaution: Product has not been fully validated for medical application