| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
M1 muscarinic acetylcholine receptor (M1 mAChR / CHRM1). EC50: 1.38 µM for M1 mAChR positive allosteric modulation. Does not cross-react with other muscarinic receptors (M2-M5).
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|---|---|
| ln Vitro |
ML169 (VU0405652) does not exhibit orthotopic binding at M1–M5, and it is selective for biogenic amines (D2, H-HT2B, etc.) [1]. APP processing is redirected by ML169 into non-amyloidogenic pathways [1]. The release of non-amyloid APPsa mediated by carbachol (CCh) is enhanced by ML169 (2 µM) to an equivalent degree as 10 µM CCh [1].
Potentiates carbachol (CCh)-mediated non-amyloidogenic APPsa release at 2 µM to the same degree as 10 µM CCh. Shifts APP processing towards a non-amyloidogenic pathway. Selective versus biogenic amines (D2, 5-HT2B, etc.) with no orthosteric binding at M1-M5. |
| ln Vivo |
Rats given 10 mg/kg; ip dose of ML169 (VU0405652) showed a brain AUC/plasma AUC of 0.32 after 1 hour [1].
Demonstrates brain penetration with brain AUC/plasma AUC ratio of 0.32 at 1 hour following intraperitoneal administration at 10 mg/kg in rats. Supports both acute and chronic in vivo paradigms in Alzheimer's and schizophrenia models. |
| Enzyme Assay |
M1 mAChR-expressing cell membranes are incubated with ML169 and a radiolabeled orthosteric ligand in binding buffer. Allosteric modulation is assessed by measuring the compound's effect on orthosteric ligand binding affinity or by functional assays measuring receptor activation in membrane preparations.
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| Cell Assay |
Chinese hamster ovary (CHO) cells expressing rat M1 receptor are treated with ML169 at various concentrations. Calcium mobilization is measured using fluorescent calcium indicators to determine EC50 values for positive allosteric modulation. APP processing and amyloidogenic pathway modulation are assessed in relevant cell lines.
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| Animal Protocol |
ML169 is administered to rats via intraperitoneal (10 mg/kg) or oral routes. Brain and plasma samples are collected at multiple time points. Brain/plasma AUC ratios are calculated to assess blood-brain barrier penetration and central nervous system exposure.
|
| References |
[1]. Reid PR, et al. Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): the development of ML169, an MLPCN probe. Bioorg Med Chem Lett. 2011 May 1;21(9):2697-701.
|
| Molecular Formula |
C21H17BRFN3O4S
|
|---|---|
| Molecular Weight |
506.35
|
| Exact Mass |
505.011
|
| CAS # |
1222878-02-5
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| PubChem CID |
44475955
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
5.453
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
31
|
| Complexity |
751
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC(=NO1)NC(=O)CS(=O)(=O)C2=CN(C3=CC=CC=C32)CC4=C(C=CC(=C4)Br)F
|
| InChi Key |
RUYRNYRGPSAXTK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H17BrFN3O4S/c1-13-8-20(25-30-13)24-21(27)12-31(28,29)19-11-26(18-5-3-2-4-16(18)19)10-14-9-15(22)6-7-17(14)23/h2-9,11H,10,12H2,1H3,(H,24,25,27)
|
| Chemical Name |
2-[1-[(5-bromo-2-fluorophenyl)methyl]indol-3-yl]sulfonyl-N-(5-methyl-1,2-oxazol-3-yl)acetamide
|
| Synonyms |
ML 169 ML-169ML169
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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 | 1.9749 mL | 9.8746 mL | 19.7492 mL | |
| 5 mM | 0.3950 mL | 1.9749 mL | 3.9498 mL | |
| 10 mM | 0.1975 mL | 0.9875 mL | 1.9749 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00742820 | COMPLETED | Drug: Calcium Acetate Oral Solution 667 mg per 5 mL Drug: Calcium Acetate 667 mg GelCaps Dietary Supplement: Calcium Citrate 950 mg Caplets |
Hyperphosphatemia | Fresenius Medical Care North America | 2008-08 | Phase 1 |
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