ML382

Research use only, not for human use.

ML382 is a potent and selective MrgX1 positive allosteric modulator(EC50 : 190 nM).ML382 enhances the ability of BAM8-22 to inhibit high-voltage-activated Ca2+ channels and attenuate spinal nociceptive transmission, both BAM8-22 and ML382 effectively attenuated evoked, persistent, and spontaneous pain without causing obvious side effects.

ML382 is a potent and selective MrgX1 positive allosteric modulator(EC50 : 190 nM).ML382 enhances the ability of BAM8-22 to inhibit high-voltage-activated Ca2+ channels and attenuate spinal nociceptive transmission, both BAM8-22 and ML382 effectively attenuated evoked, persistent, and spontaneous pain without causing obvious side effects. Notably, ML382 by itself attenuated both evoked pain hypersensitivity and spontaneous pain in MrgprX1 mice after nerve injury without acquiring coadministration of an exogenous agonist.

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.

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.

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Others

Other Targets

MrgX1

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1646499-97-9

360.42

C??H??NO?

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (277.45 mM)

CCOc1ccccc1NC(=O)c1ccccc1NS(=O)(=O)C1CC1

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(-20℃)

With Ice Pack

≥ 2 years