| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
ML382 specifically targets Mas-related G protein-coupled receptor X1 (MRGPRX1/MrgX1), a receptor involved in pain sensation and itch. As a positive allosteric modulator, it binds to an allosteric site on the receptor to enhance the efficacy of orthosteric agonists such as BAM8-22.
|
|---|---|
| ln Vitro |
BAM8-22 suppresses ICa with an IC50 of 0.66 ± 0.05 μM when ML382 is not present. The BAM8-22 IC50 dropped to 0.43 ± 0.02 μM, 0.25 ± 0.02 μM, 0.06 ± 0.01 μM, and 0.08 ± 0.01 μM in the presence of 0.1 μM, 1 μM, 10 μM, and 30 μM ML382, respectively. Therefore, ML382 dose-dependently boosted the potency of BAM8-22, further revealing that ML382 is a positive allosteric modulator of MRGPRX1 [1]. Lower IC50 generally indicates higher potency.
In vitro, ML382 acts as a positive allosteric modulator of MRGPRX1 with an EC50 of 190 nM in cell-based calcium imaging assays. It enhances BAM8-22-induced inhibition of high-voltage-activated calcium channels and attenuates spinal nociceptive transmission. These effects are consistent with its role in modulating pain signaling pathways. |
| ln Vivo |
In MrgprX1 mouse DRG neurons, ML382 (5 μM) markedly enhanced the suppression of ICa induced by low concentrations of BAM8-22 (0.5 μM). In MrgprX1 mice, ML382 increases BAM8-22 inhibition of spinal synaptic transmission. ML382 (25 μM, 125 μM, and 250 μM; 5 μL; i.th.;) attenuates heat hypersensitivity in MrgprX1 mice in a dose-dependent manner. When compared to pretreatment values, ML382 (lumbar puncture injection; 25 μM, 5 μL) led to a significantly longer posttreatment duration in the ML382-paired chamber. In MrgprX1 mice, ML382 reduces chronic pain brought on by nerve damage [1].
In vivo, ML382 has been shown to attenuate both evoked pain hypersensitivity and spontaneous pain in MrgprX1-expressing mice. Both BAM8-22 and ML382 effectively reduce evoked, sustained, and spontaneous pain without causing significant side effects. These findings support the therapeutic potential of MRGPRX1 modulation for pain management. |
| Enzyme Assay |
The in vitro activity of ML382 is assessed using cell-based calcium imaging assays in cells expressing MRGPRX1. Cells are loaded with a calcium-sensitive fluorescent dye, and the change in intracellular calcium concentration is measured upon addition of ML382 in the presence or absence of the agonist BAM8-22. The EC50 for positive allosteric modulation is determined by plotting the response against compound concentration.
|
| Cell Assay |
Cellular assays for ML382 utilize cell lines stably or transiently expressing human MRGPRX1. The compound's ability to modulate receptor activity is measured using calcium flux assays. Cells are pre-incubated with ML382 at various concentrations, and receptor activation is triggered by the addition of BAM8-22. The potentiation of the calcium response is quantified to determine the EC50 for allosteric modulation.
|
| Animal Protocol |
In vivo efficacy of ML382 is evaluated in mouse models of pain. MrgPRX1 transgenic mice are used to assess the analgesic effects of ML382. The compound is administered via intraperitoneal or intravenous injection, and pain responses are measured using assays such as the formalin test, von Frey test for mechanical allodynia, and Hargreaves test for thermal hyperalgesia.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of ML382 have not been fully characterized in the public domain. It has a molecular weight of 360.43 g/mol and a molecular formula of C18H20N2O4S. Solubility data indicate it is soluble in DMSO (>25 mg/ml) and ethanol (5 mg/mL with warming). Further ADME studies are needed.
|
| Toxicity/Toxicokinetics |
Toxicology data for ML382 are limited. In vivo studies in mice indicate that ML382 does not cause significant side effects at efficacious doses. Comprehensive toxicological assessments, including hERG, genotoxicity, and repeated-dose toxicity studies, have not been published.
|
| References |
|
| Additional Infomation |
ML382 is a research tool developed for studying MRGPRX1 biology and pain modulation. It has not entered clinical trials. Its mechanism as a positive allosteric modulator offers a promising approach for pain therapy by enhancing endogenous analgesic pathways without directly activating the receptor.
|
| Molecular Formula |
C18H20N2O4S
|
|---|---|
| Molecular Weight |
360.42
|
| Exact Mass |
360.114
|
| Elemental Analysis |
C, 59.98; H, 5.59; N, 7.77; O, 17.76; S, 8.89
|
| CAS # |
1646499-97-9
|
| PubChem CID |
71598556
|
| Appearance |
White to off-white solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Index of Refraction |
1.631
|
| LogP |
3.27
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
25
|
| Complexity |
556
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S(C1CC1)(NC1=CC=CC=C1C(NC1C=CC=CC=1OCC)=O)(=O)=O
|
| InChi Key |
RCSLEKLNDJJJLF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H20N2O4S/c1-2-24-17-10-6-5-9-16(17)19-18(21)14-7-3-4-8-15(14)20-25(22,23)13-11-12-13/h3-10,13,20H,2,11-12H2,1H3,(H,19,21)
|
| Chemical Name |
2-(cyclopropylsulfonylamino)-N-(2-ethoxyphenyl)benzamide
|
| Synonyms |
ML 382; ML-382; ML382
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~277.45 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.94 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 (6.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7745 mL | 13.8727 mL | 27.7454 mL | |
| 5 mM | 0.5549 mL | 2.7745 mL | 5.5491 mL | |
| 10 mM | 0.2775 mL | 1.3873 mL | 2.7745 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
