| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
The primary target of the active parent compound ML375 is the muscarinic acetylcholine receptor subtype 5 (M5 mAChR), where it acts as a potent and highly selective negative allosteric modulator (NAM). In contrast, the (R)-enantiomer is reported to be devoid of any significant activity at the human M5 receptor, with an IC50 value greater than 30 microM, confirming its role as an inactive comparator. This lack of affinity for the intended M5 receptor makes it a valuable negative control for elucidating the target-specific pharmacology of the ML375 scaffold.
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| ln Vitro |
The (R)-ML375 enantiomer is specifically characterized by its lack of activity at the M5 receptor. While the parent compound ML375 exhibits sub-micromolar potency in vitro (human M5 IC50 = 300 nM, rat M5 IC50 = 790 nM), (R)-ML375 demonstrates an IC50 of greater than 30 microM at the human M5 receptor, indicating it is essentially inactive. This clear distinction in in vitro potency underscores the enantioselective nature of the modulatory effect and establishes (R)-ML375 as a critical negative control for in vitro assays designed to characterize the M5 NAM activity of the S-enantiomer.
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| ln Vivo |
The (R)-ML375 enantiomer is not characterized for in vivo activity; it serves as an inactive control. In vivo studies with the active enantiomer, ML375, have demonstrated its efficacy in rodent models of substance use disorder. For instance, ML375 (10-30 mg/kg, administered intraperitoneally) has been shown to attenuate the reinforcing effects of cocaine, and it is known to reduce self-administration of ethanol and oxycodone in rat models, supporting the M5 receptor as a target for addiction therapy.
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| Enzyme Assay |
Due to its lack of activity at the M5 receptor, there are no specific binding protocols for (R)-ML375 beyond its use as a negative control. For the active parent ML375, a binding assay protocol would typically involve radioligand binding studies to determine its allosteric binding site. One such study used radioligand binding and functional assays to show that ML375 does not interact with common mAChR allosteric sites. Molecular docking and site-directed mutagenesis helped identify its binding site at the interface of transmembrane domains 2-4 of the M5 receptor.
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| Cell Assay |
Detailed, standardized cell-based assay protocols are not publicly available for (R)-ML375. For the active parent compound ML375, cell-based assays typically involve measuring its functional effect on calcium mobilization in CHO cells transfected with the human or rat M5 receptor. ML375 is known to act as a negative allosteric modulator, and this effect has been confirmed in inositol phosphate (IP) accumulation assays after receptor reserve is reduced by an alkylating agent like phenoxybenzamine.
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| Animal Protocol |
(R)-ML375 itself is not used in animal studies as a pharmacologically active agent. As the negative control, it would be administered to animals to rule out off-target effects observed with the active compound. For the parent compound ML375, a typical in vivo experiment involves administering it to rats (e.g., 10-30 mg/kg, i.p.) prior to behavioral tests, such as self-administration or cue-reactivity models of drug-seeking behavior, to evaluate its effect on substance use disorders.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for the (R)-ML375 enantiomer have not been reported. However, the active S-enantiomer, ML375, is noted for its excellent multispecies pharmacokinetic profile, which includes high CNS penetration (brain:plasma ratio Kp = 1.8) and oral bioavailability. In rats, ML375 exhibits low plasma clearance (2.5 mL/min/kg) but an exceptionally long terminal elimination half-life of approximately 80 hours, a property that can be challenging for certain addiction study designs but useful for sustained exposure experiments.
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| Toxicity/Toxicokinetics |
There is no publicly available toxicological data for (R)-ML375. For the structurally related active parent compound ML375, safety data primarily come from material safety data sheets. These indicate that under fire conditions, ML375 may decompose and emit toxic fumes. General safety precautions include avoiding release into the environment and using proper personal protective equipment when handling, as no specific acute or repeated-dose toxicity data have been reported in scientific literature.
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| References | |
| Additional Infomation |
(R)-ML375 is strictly a research tool and is not approved for therapeutic use. It has not entered any clinical trials. Its primary value lies in serving as the enantiomeric negative control for the active M5 NAM, ML375. Research on M5 negative allosteric modulators, including the parent ML375, is focused on preclinical models of neuropsychiatric disorders such as substance use disorder (opioid, cocaine, and alcohol addiction). By modulating M5 receptors in the brain's reward pathway, these compounds are being explored for their potential to reduce drug-seeking and relapse behaviors, representing a promising non-opioid strategy for addiction treatment.
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| Molecular Formula |
C23H15CLF2N2O2
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| Molecular Weight |
424.83
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| CAS # |
1488362-56-6
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| Appearance |
Solid powder
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| Synonyms |
(R)-VU0483253
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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 (235.39 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.88 mM) in 10% DMSO 40% PEG300 5% Tween-80 45% Saline (these cosolvents are added from left to right, one by one), clear solution; ultrasonic dissolution can obtain a 2.5 mg/mL clear solution.
For example, if 1 mL of working solution, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well; then add 50 μL Tween-80 to the above system and mix well; then continue to add 450 μL saline to make up to 1 mL. *Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in 100 mL of ddH₂O to obtain a clear solution. Solubility in formula 2: 2.5 mg/mL (5.88 mM) in 10% DMSO 90% Corn Oil (these co-solvents are added one by one from left to right), clear solution; Ultrasonic dissolution can obtain a 2.5 mg/mL clear solution. This solution can be used as appropriate for animal experiments with an experimental period of more than half a month. . For example, if you need to prepare 1 mL of working solution, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3539 mL | 11.7694 mL | 23.5388 mL | |
| 5 mM | 0.4708 mL | 2.3539 mL | 4.7078 mL | |
| 10 mM | 0.2354 mL | 1.1769 mL | 2.3539 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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