For research use only. Not for therapeutic Use.
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[1].
ML375 (10-30 mg/kg; i.p.; once) attenuates both the reinforcing effects and the relative strength of cocaine[2].
ML375 exhibits low clearance (CLp, 2.5 mL/min/kg) and a long elimination half-life (T1/2, 80 hr) in rodents (male, Sprague-Dawley rat, 1 mg/kg IV,) and nonhuman primates (male, cynomolgus monkey, 1 mg/kg, CLp, 3.0 mL/min/kg, T1/2, 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 (Cmax) of 1.4 μM and a corresponding time to reach Cmax (Tmax) of 7 hours[1].
| Catalog Number | I044354 |
| CAS Number | 1488362-55-5 |
| Synonyms | (9bS)-9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydroimidazo[2,1-a]isoindol-5-one |
| Molecular Formula | C23H15ClF2N2O2 |
| Purity | ≥95% |
| InChI | InChI=1S/C23H15ClF2N2O2/c24-16-8-6-15(7-9-16)23-18-4-2-1-3-17(18)22(30)28(23)12-11-27(23)21(29)14-5-10-19(25)20(26)13-14/h1-10,13H,11-12H2/t23-/m0/s1 |
| InChIKey | GXBAKXRLQAPKEE-QHCPKHFHSA-N |
| SMILES | C1CN(C2(N1C(=O)C3=CC=CC=C32)C4=CC=C(C=C4)Cl)C(=O)C5=CC(=C(C=C5)F)F |
| Reference | [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. [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. |
