Art. -Nr.: HY-12567

ML375

(Synonyms: VU0483253)

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ML375 (VU0483253) is a potent, highly selective, brain-penetrant and orally active M5 mAChR negative allosteric modulator (NAM) with IC₅₀s of 300 nM and 790 nM for human and rat M5, respectively. ML375 is inactive at human and rat M1-M4.

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Reinheit: 99.64%
CAS. Nr.: 1488362-55-5
Formel: C₂₃H₁₅ClF₂N₂O₂
Molecular Weight:424.83

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

ML375 Chemical Structure

CAS. Nr.: 1488362-55-5

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target

mAChR5

Alle mAChR Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	IC₅₀	>30 μM Compound: 8, ML375, VU0483253	Negative allosteric modulation of human muscarinic acetylcholine receptor M1 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl Negative allosteric modulation of human muscarinic acetylcholine receptor M1 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl	[PMID: 24164599]
CHO	IC₅₀	>30 μM Compound: 8, ML375, VU0483253	Negative allosteric modulation of human muscarinic acetylcholine receptor M2 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl Negative allosteric modulation of human muscarinic acetylcholine receptor M2 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl	[PMID: 24164599]
CHO	IC₅₀	>30 μM Compound: 8, ML375, VU0483253	Negative allosteric modulation of human muscarinic acetylcholine receptor M3 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl Negative allosteric modulation of human muscarinic acetylcholine receptor M3 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl	[PMID: 24164599]
CHO	IC₅₀	>30 μM Compound: 8, ML375, VU0483253	Negative allosteric modulation of human muscarinic acetylcholine receptor M4 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl Negative allosteric modulation of human muscarinic acetylcholine receptor M4 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl	[PMID: 24164599]
CHO	IC₅₀	>30 μM Compound: 8, ML375, VU0483253	Negative allosteric modulation of rat muscarinic acetylcholine receptor M1 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo Negative allosteric modulation of rat muscarinic acetylcholine receptor M1 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo	[PMID: 24164599]
CHO	IC₅₀	>30 μM Compound: 8, ML375, VU0483253	Negative allosteric modulation of rat muscarinic acetylcholine receptor M2 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo Negative allosteric modulation of rat muscarinic acetylcholine receptor M2 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo	[PMID: 24164599]
CHO	IC₅₀	>30 μM Compound: 8, ML375, VU0483253	Negative allosteric modulation of rat muscarinic acetylcholine receptor M3 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo Negative allosteric modulation of rat muscarinic acetylcholine receptor M3 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo	[PMID: 24164599]
CHO	IC₅₀	>30 μM Compound: 8, ML375, VU0483253	Negative allosteric modulation of rat muscarinic acetylcholine receptor M4 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo Negative allosteric modulation of rat muscarinic acetylcholine receptor M4 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo	[PMID: 24164599]
CHO	IC₅₀	300 nM Compound: 8, ML375, VU0483253	Negative allosteric modulation of human muscarinic acetylcholine receptor M5 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl Negative allosteric modulation of human muscarinic acetylcholine receptor M5 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fl	[PMID: 24164599]
CHO	IC₅₀	790 nM Compound: 8, ML375, VU0483253	Negative allosteric modulation of rat muscarinic acetylcholine receptor M5 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo Negative allosteric modulation of rat muscarinic acetylcholine receptor M5 expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization incubated for 150 secs prior to acetylcholine induction by Fluo-4 AM staining-based fluo	[PMID: 24164599]

In Vivo

ML375 (10-30 mg/kg; i.p.; once) attenuates both the reinforcing effects and the relative strength of cocaine^[2].
ML375 exhibits low clearance (CL_p, 2.5 mL/min/kg) and a long elimination half-life (T_1/2, 80 hr) in rodents (male, Sprague-Dawley rat, 1 mg/kg IV,) and nonhuman primates (male, cynomolgus monkey, 1 mg/kg, CL_p, 3.0 mL/min/kg, T_1/2, 10 hr)^[1].
ML375 also demonstrates high oral bioavailability (%F, 80) following administration of a suspension-dose to male SD rats with a maximal plasma concentration (C_max) of 1.4 μM and a corresponding time to reach C_max (T_max) of 7 hours^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Male Sprague-Dawley rats (70 days old; 260-300 g) injected with cocaine^[2]
Dosage:

10 mg/kg, 30 mg/kg
Administration:

i.p.; once
Result:

Produced dose-related reductions in cocaine self-administration.

Chemical Information

CAS. Nr. 1488362-55-5
Appearance Solid
Molecular Weight 424.83
Formel C₂₃H₁₅ClF₂N₂O₂
Color White to off-white
SMILES

O=C1N2[C@@](N(C(C3=CC=C(F)C(F)=C3)=O)CC2)(C4=CC=C(Cl)C=C4)C5=C1C=CC=C5
Synonyms

VU0483253
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 40 mg/mL (94.16 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

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

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 5 mg/mL (11.77 mM); Clear solution

This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (282 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Patrick R Gentry, et al. Discovery of the first M5-selective and CNS penetrant negative allosteric modulator (NAM) of a muscarinic acetylcholine receptor: (S)-9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-one (ML375). J Med Chem. 2013 Nov 27;56(22):9351-5. [Content Brief]

[2]. Barak W Gunter, et al. Selective inhibition of M 5 muscarinic acetylcholine receptors attenuates cocaine self-administration in rats. Addict Biol. 2018 Sep;23(5):1106-1116. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.3539 mL	11.7694 mL	23.5388 mL	58.8471 mL
	5 mM	0.4708 mL	2.3539 mL	4.7078 mL	11.7694 mL
	10 mM	0.2354 mL	1.1769 mL	2.3539 mL	5.8847 mL
	15 mM	0.1569 mL	0.7846 mL	1.5693 mL	3.9231 mL
	20 mM	0.1177 mL	0.5885 mL	1.1769 mL	2.9424 mL
	25 mM	0.0942 mL	0.4708 mL	0.9416 mL	2.3539 mL
	30 mM	0.0785 mL	0.3923 mL	0.7846 mL	1.9616 mL
	40 mM	0.0588 mL	0.2942 mL	0.5885 mL	1.4712 mL
	50 mM	0.0471 mL	0.2354 mL	0.4708 mL	1.1769 mL
	60 mM	0.0392 mL	0.1962 mL	0.3923 mL	0.9808 mL
	80 mM	0.0294 mL	0.1471 mL	0.2942 mL	0.7356 mL

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ML375

GPCR/G Protein Compound Library

Neuronal Signaling Compound Library

CNS-Penetrant Compound Library

Orally Active Compound Library

Neurotransmitter Receptor Compound Library

Anti-Parkinson's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Heterocyclic Compound Library

Membrane Protein-targeted Compound Library

Membrane Receptor-targeted Compound Library

Highly Selective Inhibitors Library

Allosteric Modulators (AMs) Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Lactylation Compound Library

Alle mAChR Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

ML375

GPCR/G Protein Compound Library

Neuronal Signaling Compound Library

CNS-Penetrant Compound Library

Orally Active Compound Library

Neurotransmitter Receptor Compound Library

Anti-Parkinson's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Heterocyclic Compound Library

Membrane Protein-targeted Compound Library

Membrane Receptor-targeted Compound Library

Highly Selective Inhibitors Library

Allosteric Modulators (AMs) Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Lactylation Compound Library

Alle mAChR Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

ML375 Related Classifications

HY-12567 Related Classifications