SAGE-217

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

SAGE-217 (Zuranolone, SAGE217) 是一种有效的口服活性 GABAA 受体正变构调节剂，对于 α1β2γ2 和 α4β3δ GABAA 受体的 EC50 分别为 296 和 163 nM。

SAGE-217 (Zuranolone, SAGE217) is a potent, orally active GABAA receptor positive allosteric modulator with EC50 of 296 and 163 nM for α1β2γ2 and α4β3δ GABAA r eceptors, respectively; effectively reduces pentylenetretazol (PTZ)-induced seizures in mice, abolishes both behavioral and electrographic seizure activity.Depression Phase 3 Clinical(In Vitro):Zuranolone is a potent GABAA receptor agonist with EC50s of 296 and 163 nM for α1β2γ2 and α4β3δ GABAA receptors, respectively. Zuranolone is currently being studied in parallel phase 2 clinical trials for the treatment of postpartum depression (PPD) and major depressive disorder (MDD). Zuranolone shows >30 μM inhibition in a cardiac panel of eight relevant cardiac ion channels. At 10 μM concentration of Zuranolone, only binding at the glycine (57%), sigma receptors (88%), and inhibition of the transient receptor potential vanilloid 1 (TRPV1, 95%) is noted.(In Vivo):Acute administration of Zuranolone (0.3 to 10 mg/kg, ip) effectively reduces pentylenetretazol (PTZ)-induced seizures in mice (MECplasma=85 nM) as well as produces a dose-dependent anticonvulsant effect in the mouse 6 Hz electrical stimulation model. In the rat model of status epilepticus (SE), Zuranolone (0.3 to 5 mg, iv) abolishes both behavioral and electrographic seizure activity, even when administered 60 min after induction of SE. Additional PK studies of Zuranolone in dog show low clearance (<10% of hepatic blood flow), resulting in excellent oral bioavailability (F=68%).

Zuranolone is a potent GABAA receptor agonist with EC50s of 296 and 163 nM for α1β2γ2 and α4β3δ GABAA receptors, respectively. Zuranolone is currently being studied in parallel phase 2 clinical trials for the treatment of postpartum depression (PPD) and major depressive disorder (MDD). Zuranolone shows >30 μM inhibition in a cardiac panel of eight relevant cardiac ion channels. At 10 μM concentration of Zuranolone, only binding at the glycine (57%), sigma receptors (88%), and inhibition of the transient receptor potential vanilloid 1 (TRPV1, 95%) is noted.

Acute administration of Zuranolone (0.3 to 10 mg/kg, ip) effectively reduces pentylenetretazol (PTZ)-induced seizures in mice (MECplasma=85 nM) as well as produces a dose-dependent anticonvulsant effect in the mouse 6 Hz electrical stimulation model. In the rat model of status epilepticus (SE), Zuranolone (0.3 to 5 mg, iv) abolishes both behavioral and electrographic seizure activity, even when administered 60 min after induction of SE. Additional PK studies ofZuranolone in dog show low clearance (<10% of hepatic blood flow), resulting in excellent oral bioavailability (F=68%).

Zuranolone | SAGE217

Membrane Transporter/Ion Channel

GAT

GAT

Neurological Disease

Depression

1632051-40-1

409.574

C25H35N3O2

>98% (HPLC)

DMSO : ≥ 100 mg/mL. 244.16 mM

CC1(CCC2C(C1)CCC3C2CCC4(C3CCC4C(=O)CN5C=C(C=N5)C#N)C)O

1-[2-[(3R,5R,8R,9R,10S,13S,14S,17S)-3-hydroxy-3,13-dimethyl-2,4,5,6,7,8,9,10,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl]pyrazole-4-carbonitrile

(-20℃)

With Ice Pack

≥ 2 years