SUVN-G3031 dihydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SUVN-G3031 (SUVN-G 3031) 是一种有效的、选择性的、口服活性的组胺 H3 受体 (H3R) 反向激动剂，Ki 为 8.73 nM (hH3R)。

SUVN-G3031 (SUVN-G 3031) is a potent, selective, orally active histamine H3 receptor (H3R) inverse agonist with Ki of 8.73 nM (hH3R); exhibited an IC50 of 20 nM with progressive inhibition of (R)-α-methylhistamine (0.03 μM) induced agonist activity in [35S]-GTPγS binding assay using CHO-K1 cells expressing human H3R membranes; reverses (R)-α-methylhistamine induced dipsogenia in vivo.Parkinson Disease Phase 1 Clinical.

Samelisant displays inverse agonist activity and it exhibits very high selectivity towards H3R. The pEC50 value of histamine (8.5) for human H3 receptor increases to 8.2, 7.3 and 6.2 after treatment with 1, 10 and 100 nM of Samelisant, respectively. The pEC50 value of histamine (8.2) for rat H3 receptor increases to 7.9, 7.4 and 6.4 after treatment with 1, 10 and 100 nmol/L of Samelisant, respectively.Samelisant binds to the orthosteric site in a reversible manner with Kb values of 1.3 nM and 1.1 nM deduced from pA2 value for human and rat H3R, respectively.Samelisant also modulates dopamine and norepinephrine levels in the cerebral cortex while it has no effects on dopamine levels in the striatum or nucleus accumbens.

Treatment with Samelisant (10 and 30 mg/kg, p.o.) produces a significant increase in wakefulness with a concomitant decrease in non-rapid eye movement sleep (NREM) sleep in orexin knockout mice subjected to sleep electroencephalography (EEG). Samelisant also produces a significant decrease in direct rapid eye movement (REM) sleep onset (DREM) episodes, demonstrating its anticataplectic effects in an animal model relevant to narcolepsy.Samelisant treatment in mice produces a dose-dependent increase in tele-methylhistamine levels indicating the activation of histaminergic neurotransmission. Animal Model:Male Wistar rats or male C57BL6J mice Dosage:1, 3, 10, and 30 mg/kg Administration:Oral administration Result:Produced a dose-dependent increase in t-MH levels in the frontal cortex, hypothalamus and cerebrospinal fluid (CSF) of male Wistar rats.Produced a significant increase in t-MH levels of the frontal cortex, striatum and hypothalamus in mice.

SUVN-G 3031

GPCR/G Protein

Histamine Receptor

Histamine Receptor

Neurological Disease

Parkinson Disease

1394808-20-8

446.413

C21H33Cl2N3O3

>98% (HPLC)

In Vitro:?DMSO : 62.5 mg/mL (140.01 mM)

C1CC(C1)N2CCC(CC2)OC3=CC=C(C=C3)NC(=O)CN4CCOCC4.Cl.Cl

N-[4-(l-Cyclobutylpiperidin-4-yloxy) phenyl]-2-(morpholin-4-yl) acetamide dihydrochloride

(-20℃)

With Ice Pack

≥ 2 years