Synonym
ML352; ML-352; ML 352; VU0476201; VU-0476201; VU 0476201; VU0476328; VU-0476328; VU 0476328;
IUPAC/Chemical Name
N-((3-isopropylisoxazol-5-yl)methyl)-4-methoxy-3-((1-methylpiperidin-4-yl)oxy)benzamide
InChi Key
WBLVOWHFRUAMCP-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=C(NCC1=CC(C(C)C)=NO1)C2=CC=C(OC)C(OC3CCN(C)CC3)=C2
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
ML352 is a noncompetitive inhibitor of the presynaptic choline transporter (CHT) with Ki values of 92 and 166 nM for HEK293 cells.
In vitro activity:
First, this study sought to confirm the potency and specificity of ML352 for inhibition of hCHT LV-AA in transfected HEK 293 cells. These studies (Figure 3A) found that ML352 inhibited [3H]choline uptake with high affinity (Ki = 92 ± 2.8 nM), with data well-fit to a single-site inhibition model (r = 0.935). Figure 4B demonstrates that ML352 choline uptake inhibition was retained when tested in mouse forebrain synaptosomes (Ki = 166 ± 12 nM).
Reference: ACS Chem Neurosci. 2015 Mar 18;6(3):417-27. https://pubmed.ncbi.nlm.nih.gov/25560927/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
20.0 |
51.62 |
|
| DMSO:PBS (pH 7.2) (1:1) |
0.5 |
1.29 |
|
| Ethanol |
5.0 |
12.90 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
387.48
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
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. doi: 10.1021/cn5001809. Epub 2015 Feb 2. PMID: 25560927; PMCID: PMC4367188.
In vitro protocol:
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. doi: 10.1021/cn5001809. Epub 2015 Feb 2. PMID: 25560927; PMCID: PMC4367188.
1: Bertron JL, Ennis EA, Tarr CJ, Wright J, Dickerson JW, Locuson CW, Blobaum AL, Rook JM, Blakely RD, Lindsley CW. Optimization of the choline transporter (CHT) inhibitor ML352: Development of VU6001221, an improved in vivo tool compound. Bioorg Med Chem Lett. 2016 Oct 1;26(19):4637-4640. doi: 10.1016/j.bmcl.2016.08.062. Epub 2016 Aug 21. PubMed PMID: 27575469.
2: Bollinger SR, Engers DW, Ennis EA, Wright J, Locuson CW, Lindsley CW, Blakely RD, Hopkins CR. Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter. Bioorg Med Chem Lett. 2015 Apr 15;25(8):1757-1760. doi: 10.1016/j.bmcl.2015.02.058. Epub 2015 Feb 28. PubMed PMID: 25801932; PubMed Central PMCID: PMC4385452.
3: 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. doi: 10.1021/cn5001809. Epub 2015 Feb 2. PubMed PMID: 25560927; PubMed Central PMCID: PMC4367188.
