| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
Targets G protein-coupled receptor 68 (GPR68, also known as OGR1) as a positive allosteric modulator (PAM). It demonstrates specificity for GPR68 over closely related proton GPCRs (such as GPR4, GPR65), neurotransmitter transporters, and the hERG ion channel. As a PAM, it is a tool to amplify and study GPR68-mediated signaling.
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| ln Vitro |
5-HT2B has a moderate binding affinity to MS48107 (compound 71) with a Ki value of 219 nM. MS48107 exhibits mild antagonist activity at 5-HT2B receptors, with a Ki value of 310 nM, but no agonist activity at these receptors[1]. Compound 71, MS48107, has agonistic action exclusively at the MT1 and MT2 receptors. At the MT1 receptor, MS48107 has mild complete agonist activity (EC50 = 320 nM), while at the MT2 receptor, its partial agonist activity is weak (EC50 = 540 nM). has modest affinity for binding to the MT1 (5900 nM) and MT2 (1100 nM) receptors[1].
As a PAM, MS48107 itself does not activate GPR68 on its own. Instead, it binds to a site distinct from the orthosteric (agonist) site and increases the receptor‘s sensitivity and maximal response to acidic pH (protons). This allows researchers to potentiate GPR68 signaling in a more physiologically relevant, context-dependent manner, as the receptor is only active when pH is low. |
| ln Vivo |
A single intraperitoneal injection at a dose of 25 mg/kg for MS48107 (compound 71) causes high exposure levels (above 10 μM) in the brain and plasma within 0.5 hours in mice (Swiss Albino mice). For two hours, the high levels of compound exposure are sustained in the brain and plasma[1].
Detailed in vivo activity data for MS48107 is not publicly available. Because it is a PAM that works by amplifying responses to endogenous acidosis, it could be a powerful tool in animal models where tissue acidosis is a key feature (e.g., ischemic stroke, traumatic brain injury, cancer, and inflammatory pain) to determine if amplifying GPR68 signals is protective or damaging. |
| Enzyme Assay |
Since MS48107 is a PAM, traditional cell-free binding assays may not capture its allosteric mechanism. Its activity is defined by its ability to potentiate the response of GPR68 to a proton (agonist) challenge. This is measured using functional cellular assays (e.g., measuring inositol phosphate accumulation or calcium mobilization) rather than direct binding to membranes.
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| Cell Assay |
The functional activity of MS48107 is assessed using cells that stably express GPR68 and the G protein Galphaq. Cells are loaded with a calcium-sensitive dye and pre-incubated with varying concentrations of the PAM. They are then stimulated with a sub-maximal concentration of protons (e.g., a buffer of pH 6.8), and the resulting increase in fluorescence is measured. The enhancement of the calcium response compared to DMSO control is used to characterize the PAM activity.
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| Animal Protocol |
No specific animal studies for MS48107 are publicly available. A potential model would be a mouse model of middle cerebral artery occlusion (MCAO) for stroke. MS48107 could be administered systemically (IP or IV) to assess its ability to cross the BBB. Endpoints would include infarct volume, neurological deficit scores, and possibly the measurement of brain pH.
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| ADME/Pharmacokinetics |
Detailed PK data for MS48107 is not publicly available. It has been shown to effectively cross the blood-brain barrier (BBB) in mice, a key property for studying CNS-related functions of GPR68. Its molecular weight is 417.44, and it is formulated in solvents like DMSO and PEG300 for in vivo use.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for MS48107. As a highly selective PAM of GPR68 that is brain penetrant, its safety profile is not known. However, because it is a modulator and not a direct agonist, it is expected to have a better safety profile and lower risk of over-activation than a full agonist, making it an attractive tool for in vivo studies.
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| References | |
| Additional Infomation |
MS48107 is a research-grade chemical and is not approved for clinical use. It is a first-in-class tool compound for studying the role of the pH-sensing GPR68 receptor in the brain, where it has been implicated in memory, anxiety, and neuroinflammation, and in peripheral tissues, where it is involved in inflammation and pain.
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| Molecular Formula |
C23H20FN5O2
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|---|---|
| Molecular Weight |
417.44
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| Exact Mass |
417.16
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| CAS # |
2375070-79-2
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| PubChem CID |
139030523
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
561.7±60.0 °C at 760 mmHg
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| Flash Point |
293.5±32.9 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.659
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| LogP |
2.68
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
530
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)OC2=CC=C(C=C2)CNC3=NC(=NC(=N3)N)C4=C(C=CC=C4F)CO
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| InChi Key |
KKHDNAZPEMYUNO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H20FN5O2/c24-19-8-4-5-16(14-30)20(19)21-27-22(25)29-23(28-21)26-13-15-9-11-18(12-10-15)31-17-6-2-1-3-7-17/h1-12,30H,13-14H2,(H3,25,26,27,28,29)
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| Chemical Name |
[2-[4-amino-6-[(4-phenoxyphenyl)methylamino]-1,3,5-triazin-2-yl]-3-fluorophenyl]methanol
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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) |
DMSO: 100 mg/mL (239.56 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.99 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3956 mL | 11.9778 mL | 23.9555 mL | |
| 5 mM | 0.4791 mL | 2.3956 mL | 4.7911 mL | |
| 10 mM | 0.2396 mL | 1.1978 mL | 2.3956 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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