ML380_product_DataBase

Bioactivity

ML380 is a potent, subtype-selective, and brain-penetrant positive allosteric modulator (PAM) of M5 mAChR, with EC50s of 190 and 610 nM for human and rat M5, respectively. ML380 exhibits moderate selectivity versus the M1 and M3 mAChR subtypes. ML380 could increase the affinity of ACh for the M5 mAChR[1][2][3].

Target

IC50: 190 nM (hM5), 610 nM (rM5)

Invitro

ML380 (0.01 nM-100 μM) robustly stimulates inositol phosphate (IP) accumulation and Ca2+ mobilization in CHO-hM5 cells, with pEC50s of 5.33 and 5.71, respectively[2].ML380 (0.01-30 μM) increases the ACh-stimulated IP accumulation and Ca2+ mobilization in CHO-hM5 cells[2].

In Vivo

ML380 (1 mg/kg; i.v.) displays high clearance (66 mL/min/kg), a moderate volume of distribution (1.6 L/kg), and a short half-life (t1/2, 22 min) in rats[1].

Name

ML380

CAS

1627138-52-6

Formula

C23H25F3N4O3S

Molar Mass

494.53

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

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

Reference

[1]. Gentry PR, et, al. Development of a highly potent, novel M5 positive allosteric modulator (PAM) demonstrating CNS exposure: 1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380). J Med Chem. 2014 Sep 25;57(18 [2]. Berizzi AE, et, al. Molecular Mechanisms of Action of M5 Muscarinic Acetylcholine Receptor Allosteric Modulators. Mol Pharmacol. 2016 Oct;90(4):427-36. [3]. Berizzi AE, et, al. Structure-Activity Relationships of Pan-Gα q/11 Coupled Muscarinic Acetylcholine Receptor Positive Allosteric Modulators. ACS Chem Neurosci. 2018 Jul 18;9(7):1818-1828.

PeptideDB

ML380

CAS: 1627138-52-6 F: C23H25F3N4O3S W: 494.53