SAGE-217
(Synonyms: S-812217, SGE 797) 目录号 : GC19318
A positive allosteric modulator of GABAA receptors
Cas No.:1632051-40-1
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
SAGE-217 is a potent GABAA receptor agonist with EC50s of 296 and 163 nM for α1β2γ2 and α4β3δ GABAA receptors, respectively.
Kinase assay demonstrates that SAGE-217 is a potent GABAA receptor agonist with EC50s of 296 and 163 nM for α1β2γ2 and α4β3δ GABAA receptors, respectively. SAGE-217 is currently being studied in parallel phase 2 clinical trials for the treatment of postpartum depression (PPD) and major depressive disorder (MDD). SAGE-217 shows >30 uM inhibition in a cardiac panel of eight relevant cardiac ion channels. At 10 uM concentration of SAGE-217, only binding at the glycine (57%), sigma receptors (88%), and inhibition of the transient receptor potential vanilloid 1 (TRPV1, 95%) is noted[1].
Acute administration of SAGE-217 (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 lithium-pilocarpine model of status epilepticus (SE), SAGE-217 (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 SAGE-217 in dog show low clearance (<10% of hepatic blood flow), resulting in excellent oral bioavailability (F=68%)[1].
References:
[1]. Martinez Botella G, et al. Neuroactive Steroids. 2. 3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one (SAGE-217): A Clinical Next Generation Neuroactive Steroid Positive Allosteric Modulator of the (γ-Aminobutyric Acid)A Receptor. J Med Chem. 2017 Sep 28;60(18):7810-7819.
Animal experiment: | In vivo pharmacokinetic parameters are determined in male Sprague Dawley rats (of 200 to 300 g in weight), male CD-1 mice (15 to 25 g in weight), and male beagle dogs (8 to 12 kg in weight). Doses of Zuranolone (SAGE-217) for intravenous (IV) and oral administration (PO) are formulated as solutions in SBECD. Zuranolone (SAGE-217) is dosed IV (5 mg/kg, 2.5 mL/kg) or by oral gavage (20 mg/kg, 10 mL/kg). Animals in the IV group are sampled at 0.083, 0.25, 1, 2, 4, and 8 hours post-dose and PO animals are sampled at 0.5, 1, 2, 4, and 8 hours post dose. Brain samples from the IV group are also collected at 1 hour post-dose. Blood samples are collected into tubes treated with K2-EDTA, then centrifuged at 2000 g at 4°C for 15 min. Plasma is isolated and frozen at -70°C until extraction[1]. |
References: [1]. Martinez Botella G, et al. Neuroactive Steroids. 2. 3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one (SAGE-217): A Clinical Next Generation Neuroactive Steroid Positive Allosteric Modulator of the (γ-Aminobutyric Acid)A Receptor. J Med Chem. 2017 Sep 28;60(18):7810-7819. | |
| Cas No. | 1632051-40-1 | SDF | |
| 别名 | S-812217, SGE 797 | ||
| Canonical SMILES | O=C(CN1N=CC(C#N)=C1)[C@H]2CC[C@@]3([H])[C@]4([H])CC[C@]5([H])C[C@](C)(O)CC[C@]5([H])[C@@]4([H])CC[C@@]32C | ||
| 分子式 | C25H35N3O2 | 分子量 | 409.56 |
| 溶解度 | DMSO : ≥ 100 mg/mL (244.16 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.4416 mL | 12.2082 mL | 24.4164 mL |
| 5 mM | 0.4883 mL | 2.4416 mL | 4.8833 mL |
| 10 mM | 0.2442 mL | 1.2208 mL | 2.4416 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet