ML382

• CAT Number: I011285
• CAS Number: 1646499-97-9
• Molecular Formula: C18H20N2O4S
• Molecular Weight: 360.43
• Purity: ≥95%
• Synonyms: 2-(cyclopropylsulfonylamino)-N-(2-ethoxyphenyl)benzamide
• InChI: 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)
• InChIKey: RCSLEKLNDJJJLF-UHFFFAOYSA-N
• SMILES: CCOC1=CC=CC=C1NC(=O)C2=CC=CC=C2NS(=O)(=O)C3CC3

ML382 is a potent and selective MRGPRX1 (Mas-related G protein-coupled receptor X1, MrgX1) positive allosteric modulator, with an EC50 of 190 nM[1].
In the absence of ML382, the IC50 for BAM8-22 inhibition of ICa is 0.66 ± 0.05 μM. In the presence of 0.1 μM, 1 μM, 10 μM, and 30 μM ML382, BAM8-22 IC50 is reduced to 0.43 ± 0.02 μM, 0.25 ± 0.02 μM, 0.06 ± 0.01 μM, and 0.08 ± 0.01 μM, respectively. A lower IC50 generally indicates a higher potency; thus, ML382 dose-dependently increases the potency of BAM8–22, further demonstrating that ML382 is a positive allosteric modulator of MRGPRX1[1].
ML382 (5 μM) significantly increases inhibition of ICa by a low concentration of BAM8–22 (0.5 μM) in DRG neurons from MrgprX1 mice. ML382 enhances the inhibition of spinal synaptic transmission by BAM8-22 in MrgprX1 mice. ML382 (25 μM, 125 μM, and 250 μM; 5 μL; i.th.;) dose-dependently attenuates heat hypersensitivity in MrgprX1 mice. ML382 (lumbar puncture injection; 25 μM, 5 μL) leads to a significant increase in postconditioning time spent in the ML382-paired chamber, compared with the preconditioning value. ML382 inhibits nerve injury-induced ongoing pain in MrgprX1 mice[1].

Reference

[1]. Li Z, et al. Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain. Proc Natl Acad Sci U S A. 2017;114(10):E1996-E2005.
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[2]. Wen W, et al. Discovery and characterization of 2-(cyclopropanesulfonamido)-N-(2-ethoxyphenyl)benzamide, ML382: a potent and selective positive allosteric modulator of MrgX1. ChemMedChem. 2015;10(1):57-61.
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