ML252 hydrochloride 

ML252 hydrochloride is a selective inhibitor of KCNQ2 (Kv7.2) channel with IC₅₀s of 69 nM, 2.92 μM, 0.12 μM and 0.20 μM for KCNQ2, KCNQ1 (Kv7.1), KCNQ2/Q3 and KCNQ4, respectively. ML252 hydrochloride also inhibits Cytochrome P450 with IC₅₀s of 6.1 nM (CYP1A2), 18.9 nM (CYP2C9), 3.9 nM (CYP3A4), 19.9 nM (CYP2D6), respectively. ML252 hydrochloride shows highly brain penetrant^[1][2].

ML252 (1 μM; 0-48 h) hydrochloride shows an intrinsic clearance and subsequent predicted hepativ clearance of 1720 mL/min/kd and 67.3 mL/min/kg, respectively, in rat hepatic microsomes^[1].
ML252 (0.1-10 μM) hydrochloride inhibits the current of KCNQ2 at 0.3 μM, and completely inhibits the current at 1 μM in CHO-KCNQ2 cell line^[1].
ML252 (30 μM; 48 h) hydrochloride has no acute toxicity to CHO cells^[1].

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

ML252 (10 mg/kg, 3 mg/mL; ip; single dose; measured at 1 hr after) hydrochloride shows a highly brain penetrant with a B:P ratio of 1.9 and absolute brain levels of 672 nM in rat model^[1]. ML252 hydrochloride has the metabolic stability unsuitable for oral administration^[2].

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

344.88

C₂₀H₂₅ClN₂O

2309887-61-2

CC[C@@H](C1=CC=CC=C1)C(NC2=CC=CC=C2N3CCCC3)=O.Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Yu H, et al. Identification of a novel, small molecule inhibitor of KCNQ2 channels. 2011 Oct 28 [updated 2013 Feb 25]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–.  [Content Brief]

  [2]. Cheung YY, et al. Discovery of a series of 2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)acetamides as novel molecular switches that modulate modes of K(v)7.2 (KCNQ2) channel pharmacology: identification of (S)-2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)butanamide (ML252) as a potent, brain penetrant K(v)7.2 channel inhibitor. J Med Chem. 2012 Aug 9;55(15):6975-9.  [Content Brief]