ML352Non-competitive inhibitor of the presynaptic choline transporter CAS# 1649450-12-3 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 1649450-12-3 | SDF | Download SDF |
PubChem ID | 70679283 | Appearance | Powder |
Formula | C21H29N3O4 | M.Wt | 387.47 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | Soluble in DMSO | ||
Chemical Name | 4-methoxy-3-(1-methylpiperidin-4-yl)oxy-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]benzamide | ||
SMILES | CC(C)C1=NOC(=C1)CNC(=O)C2=CC(=C(C=C2)OC)OC3CCN(CC3)C | ||
Standard InChIKey | WBLVOWHFRUAMCP-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C21H29N3O4/c1-14(2)18-12-17(28-23-18)13-22-21(25)15-5-6-19(26-4)20(11-15)27-16-7-9-24(3)10-8-16/h5-6,11-12,14,16H,7-10,13H2,1-4H3,(H,22,25) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
ML352 Dilution Calculator
ML352 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.5808 mL | 12.9042 mL | 25.8084 mL | 51.6169 mL | 64.5211 mL |
5 mM | 0.5162 mL | 2.5808 mL | 5.1617 mL | 10.3234 mL | 12.9042 mL |
10 mM | 0.2581 mL | 1.2904 mL | 2.5808 mL | 5.1617 mL | 6.4521 mL |
50 mM | 0.0516 mL | 0.2581 mL | 0.5162 mL | 1.0323 mL | 1.2904 mL |
100 mM | 0.0258 mL | 0.129 mL | 0.2581 mL | 0.5162 mL | 0.6452 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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The neurotransmitter acetylcholine (ACh) plays a critical role in autonomic function, motor control, attention, learning, and memory, and reward. The high-affinity choline transporter (CHT) is the ratelimiting determinant of ACh synthesis, yet the transporter remains a largely undeveloped target for the detection and manipulation of synaptic cholinergic signaling. ML352 is a novel, noncompetitive inhibitor of the presynaptic choline transporter.
In vitro: At concentrations fully antagonized CHT in transfected cells and nerve terminal preparations, ML352 exhibited no inhibition of acetylcholinesterase or cholineacetyltransferase and also lacked activity at dopamine, serotonin, and norepinephrine transporters, as well as many receptors and ion channels. ML352 exhibited noncompetitive choline uptake inhibition in intact cells and reduced the apparent density of hemicholinium-3 binding sites in membrane assays, indicating allosteric transporter interactions [1].
In vivo: DMPK studies revealed a high intravenous plasma clearance, a combination of the oral bioavailability and total brain concentrations indicate ML352 to be a suitable probe for studies of altered in vivo ACh signaling and behavioral effects in rodents [2].
Clinical trial: Up to now, ML352 is still in the preclinical development stage.
Reference:
[1] Ennis EA, Wright J, Retzlaff CL, McManus OB, Lin Z, Huang X, Wu M, Li M, Daniels JS, Lindsley CW, Hopkins CR, Blakely RD. Identification and characterization of ML352: a novel, noncompetitive inhibitor of the presynaptic choline transporter. ACS Chem Neurosci. 2015 Mar 18;6(3):417-27.
[2] Elizabeth Ennis Miss, Jane Wright, James Tarr, Charles Locuson, Corey Hopkins, J Daniels, Craig Lindsley and Randy Blakely. A Novel Approach to Cholinergic Signaling Modulation: Development and Characterization of ML352, a Novel, Noncompetitive Inhibitor of the Presynaptic Choline Transporter. The FASEB Journal vol. 29 no. 1 Supplement 932.6
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Optimization of the choline transporter (CHT) inhibitor ML352: Development of VU6001221, an improved in vivo tool compound.[Pubmed:27575469]
Bioorg Med Chem Lett. 2016 Oct 1;26(19):4637-4640.
This Letter describes the further lead optimization of the CHT inhibitor probe, ML352 (VU0476201), and the development of VU6001221, an improved in vivo tool. A multi-dimensional optimization effort encountered steep SAR, and ultimately, subtle tuning of the electronics of the central phenyl core provided VU6001221, a CHT inhibitor with comparable potency for choline uptake inhibition as ML352, yet improved PK and CNS penetration. Moreover, VU6001221 enabled evaluation, for the first time, of a CHT inhibitor in a standard preclinical rodent cognition model, novel object recognition (NOR). We observed VU6001221 to elicit a dose-responsive increase in NOR, raising the possibility of agonism of synaptic alpha7 nicotinic ACh receptors by elevated extracellular choline, that if confirmed would represent a novel molecular strategy to enhance cognition.
Identification and characterization of ML352: a novel, noncompetitive inhibitor of the presynaptic choline transporter.[Pubmed:25560927]
ACS Chem Neurosci. 2015 Mar 18;6(3):417-27.
The high-affinity choline transporter (CHT) is the rate-limiting determinant of acetylcholine (ACh) synthesis, yet the transporter remains a largely undeveloped target for the detection and manipulation of synaptic cholinergic signaling. To expand CHT pharmacology, we pursued a high-throughput screen for novel CHT-targeted small molecules based on the electrogenic properties of transporter-mediated choline transport. In this effort, we identified five novel, structural classes of CHT-specific inhibitors. Chemical diversification and functional analysis of one of these classes identified ML352 as a high-affinity (Ki = 92 nM) and selective CHT inhibitor. At concentrations that fully antagonized CHT in transfected cells and nerve terminal preparations, ML352 exhibited no inhibition of acetylcholinesterase (AChE) or cholineacetyltransferase (ChAT) and also lacked activity at dopamine, serotonin, and norepinephrine transporters, as well as many receptors and ion channels. ML352 exhibited noncompetitive choline uptake inhibition in intact cells and synaptosomes and reduced the apparent density of hemicholinium-3 (HC-3) binding sites in membrane assays, suggesting allosteric transporter interactions. Pharmacokinetic studies revealed limited in vitro metabolism and significant CNS penetration, with features predicting rapid clearance. ML352 represents a novel, potent, and specific tool for the manipulation of CHT, providing a possible platform for the development of cholinergic imaging and therapeutic agents.