| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
CYP1A2 6.1 μM (IC50) CYP2C9 18.9 μM (IC50) CYP2D6 19.9 μM (IC50) CYP3A4 3.9 μM (IC50)
KCNQ2 (Kv7.2) (IC50 = 69 nM). Also inhibits KCNQ2/Q3 (IC50 = 0.12 microM), KCNQ1 (IC50 = 2.92 microM), and KCNQ4 (IC50 = 0.20 microM). |
|---|---|
| ln Vitro |
In rat liver corpuscles, the intrinsic clearance of ML252 (1 μM; 0-48 h) is 1720 mL/min/kg, while the anticipated hepatic clearance is 67.3 mL/min/kg [1]. In the CHO-KCNQ2 cell line, ML252 (0.1-0 μM) first suppresses KCNQ2 currents at 0.3 μM and then totally stops the currents at 1 μM [1]. For CHO cells, ML252 (30 μM; 48 h) does not exhibit acute toxicity [1].
ML252 is a selective KCNQ2 inhibitor with an IC50 of 69 nM. It shows selectivity over other KCNQ family members (KCNQ1, KCNQ4, KCNQ2/Q3). It is a potent CYP450 inhibitor, with IC50 values of 6.1 nM (CYP1A2), 18.9 nM (CYP2C9), 3.9 nM (CYP3A4), and 19.9 nM (CYP2D6). |
| ln Vivo |
Because of its metabolic stability, ML252 should not be used orally [2]. In the rat model, the intraperitoneal injection of ML252 (10 mg/kg, 3 mg/mL; single dose; evaluated 1 hour later) produced an absolute brain level of 672 nM and a B:P ratio of 1.9 [1].
No specific in vivo data is available. As a brain-penetrant KCNQ2 inhibitor, it would be expected to have neurological effects, potentially altering pain perception, seizure susceptibility, and cognitive function. Its potent inhibition of CYP450 enzymes suggests a high risk for drug-drug interactions in vivo. |
| Enzyme Assay |
For electrophysiology, HEK293 cells expressing human KCNQ2 channels are cultured. Whole-cell patch-clamp recordings are performed. ML252 is applied at concentrations ranging from 0.1 nM to 100 uM, and the IC50 for KCNQ2 inhibition is calculated. For CYP450 inhibition, human liver microsomes or recombinant CYP isoforms are incubated with specific probe substrates.
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| Cell Assay |
HEK293 cells expressing KCNQ2 channels are cultured in DMEM with 10% FBS. Whole-cell patch-clamp electrophysiology is performed to assess the compound's inhibitory effect. Its effect on neuronal excitability can be studied in cultured primary hippocampal or DRG neurons.
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| Animal Protocol |
ML252 is typically formulated in a suitable vehicle (e.g., 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline) and administered intraperitoneally (i.p.) to mice. Its effects on pain behavior can be assessed using models like the formalin test or by measuring mechanical allodynia.
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| ADME/Pharmacokinetics |
No specific PK data is available. The compound has a molecular weight of 308.42 and is moderately lipophilic (LogP ~3-4), suggesting good oral bioavailability and the potential to cross the blood-brain barrier. Its potent CYP450 inhibition suggests a low metabolic clearance.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available. The acute toxicity may be related to its potent inhibition of the central nervous system KCNQ2 channels, which could lead to seizures, ataxia, and cognitive impairment. Its strong CYP inhibition suggests a high risk for hepatotoxicity and drug-drug interactions.
|
| 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 . Bethesda (MD): National Center for Biotechnology Information (US); 2010–.
[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. |
| Additional Infomation |
ML252 is a research tool for studying the function of KCNQ2/Kv7.2 channels. It is useful for exploring the potential of KCNQ2 inhibitors as analgesics or anticonvulsants. However, its potent CYP inhibition complicates its use in vivo.
|
| Molecular Formula |
C20H24N2O
|
|---|---|
| Molecular Weight |
308.42
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| Exact Mass |
308.189
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| CAS # |
1392494-64-2
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| PubChem CID |
53393831
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| Appearance |
White to off-white solid powder
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| LogP |
4.557
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
372
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
Cl.O=C(C(C1C=CC=CC=1)CC)NC1=CC=CC=C1N1CCCC1
|
| InChi Key |
XBYCQOZNTLUEDX-LMOVPXPDSA-N
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| InChi Code |
InChI=1S/C20H24N2O.ClH/c1-2-17(16-10-4-3-5-11-16)20(23)21-18-12-6-7-13-19(18)22-14-8-9-15-22;/h3-7,10-13,17H,2,8-9,14-15H2,1H3,(H,21,23);1H/t17-;/m0./s1
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| Chemical Name |
(2S)-2-phenyl-N-(2-pyrrolidin-1-ylphenyl)butanamide;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2423 mL | 16.2117 mL | 32.4233 mL | |
| 5 mM | 0.6485 mL | 3.2423 mL | 6.4847 mL | |
| 10 mM | 0.3242 mL | 1.6212 mL | 3.2423 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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