| Identification | Back Directory | [Name]
ML 252 | [CAS]
1392494-64-2 | [Synonyms]
ML 252
ML252 >=98% (HPLC)
(2S)-2-phenyl-N-(2-pyrrolidin-1-ylphenyl)butanamide
(S)-2-Phenyl-N-(2-(pyrrolidin-1-yl)phenyl)butanamide
Benzeneacetamide, α-ethyl-N-[2-(1-pyrrolidinyl)phenyl]-, (αS)- | [Molecular Formula]
C20H24N2O | [MDL Number]
MFCD25976917 | [MOL File]
1392494-64-2.mol | [Molecular Weight]
308.42 |
| Hazard Information | Back Directory | [Uses]
ML252 is a selective inhibitor of KCNQ2 (Kv7.2) channel with an 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 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 shows highly brain penetrant [1][2]. | [Biological Activity]
ML252 is a potentbrain penetrant potassium channel Kv7.2 (KCNQ2) inhibitor with an IC50 of 69 nM. ML252 is only slightly selective over KCNQ3 and KCNQ4 but is over 40-fold selective for KCNQ2 vs KCNQ1unlike other KCNQ inbhibitors currently used. ML252 was also selective vs. >68 tested GPCRsion channelsand transporters. Potassium channel Kv7.2 has become a new target for Alzheimerμs Disease drug research because inhibiting it enhances acetylcholine release. SAR studies showed a small structural change from ethyl group to hydrogen resulted in a functional shift from antagonist to agonist activity (37EC50 of 170 nM)suggesting an interaction at a critical site for controlling KCNQ2 channel gating. | [in vivo]
ML252 has the metabolic stability unsuitable for oral administration[2].
ML252 (10 mg/kg, 3 mg/mL; ip; single dose; measured at 1 hr after) shows a highly brain penetrant with a B:P ratio of 1.9 and absolute brain levels of 672 nM in rat model[1]. | [IC 50]
KCNQ2: 69 nM (IC50); KCNQ1: 2.92 μM (IC50); KCNQ2/Q3: 0.12 μM (IC50); KCNQ4: 0.20 μM (IC50); CYP1A2: 6.1 μM (IC50); CYP2C9: 18.9 μM (IC50); CYP2D6: 19.9 μM (IC50); CYP3A4: 3.9 μM (IC50) | [storage]
Store at -20°C | [References]
[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–. PMID:23658963
[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. DOI:10.1021/jm300700v |
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| Company Name: |
Energy Chemical
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| Tel: |
021-58432009 400-005-6266 |
| Website: |
http://www.energy-chemical.com |
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
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