SUVN-911
目录号 : GC39575
SUVN-911 是一种高效、选择性的，有大脑通透性和口服生物活性的神经元烟碱乙酰胆碱 α4β2 受体 (α4β2 receptor) 拮抗剂，Ki 值为 1.5 nM。SUVN-911 具有抗抑郁作用。
Cas No.:2414674-71-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SUVN-911 is a potent, selective, brain penetrated and orally bioavailable neuronal nicotinic acetylcholine α4β2 receptor antagonist, with a Ki of 1.5 nM. SUVN-911 has antidepressant activity[1].
[1]. Ramakrishna Nirogi, et al. Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression. J Med Chem. 2020 Mar 26;63(6):2833-2853.
| Cas No. | 2414674-71-6 | SDF | |
| Canonical SMILES | ClC1=NC=C(OC[C@H]2N[C@@H]3C[C@@H]3C2)C=C1.[H]Cl | ||
| 分子式 | C11H14Cl2N2O | 分子量 | 261.15 |
| 溶解度 | DMSO: 125 mg/mL (478.65 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.8292 mL | 19.1461 mL | 38.2922 mL |
| 5 mM | 0.7658 mL | 3.8292 mL | 7.6584 mL |
| 10 mM | 0.3829 mL | 1.9146 mL | 3.8292 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。
Ropanicant (SUVN-911), an α4β2 nicotinic acetylcholine receptor antagonist intended for the treatment of depressive disorders: pharmacological, behavioral, and neurochemical characterization
Psychopharmacology (Berl) 2022 Jul;239(7):2215-2232.PMID:35298691DOI:10.1007/s00213-022-06108-6.
Rationale: Ropanicant (SUVN-911) (3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo (3.1.0) hexane hydrochloride) is a novel α4β2 nicotinic acetylcholine receptor (nAChR) antagonist being developed for the treatment of depressive disorders. Objectives: Pharmacological and neurochemical characterization of Ropanicant to support a potential molecule for the treatment of depressive disorders. Methods: Ropanicant was assessed for antidepressant-like activity using the rat forced swimming test (FST) and differential reinforcement of low rate -72 s (DRL-72 s). Alleviation of anhedonia was assessed in chronic mild stress model using sucrose preference test. To understand the mechanism of action, serotonin levels, ionized calcium-binding adaptor molecule 1 (Iba1), and brain-derived neurotrophic factor (BDNF) were determined. The onset of antidepressant-like activity was determined using the reduction in submissive behavior assay. The effects on cognition and sexual functions were assessed using the object recognition task and sexual dysfunction assay respectively. Interaction of Ropanicant, TC-5214, and methyllycaconitine (MLA) with citalopram was investigated individually in mice FST. Results: Ropanicant exhibited antidepressant like properties in the FST and DRL-72 s. A significant reduction in anhedonia was observed in the sucrose preference test. Oral administration of Ropanicant produced a significant increase in serotonin and BDNF levels, with a reduction in the Iba1 activity. The onset of antidepressant like effect with Ropanicant was within a week of treatment, and was devoid of cognitive dulling and sexual dysfunction. While Ropanicant potentiated the effect of citalopram in FST, such an effect was not observed with MLA or TC-5214. Conclusions: Preclinical studies with Ropanicant support the likelihood of its therapeutic utility in the treatment of depressive disorders.
Safety, Tolerability, and Pharmacokinetics of Ropanicant (SUVN-911), a Novel Alpha4 Beta2 Nicotinic Acetylcholine Receptor (α4β2 nAChR) Antagonist, in Healthy Adult and Elderly Subjects
Clin Drug Investig 2022 Sep;42(9):747-762.PMID:35963959DOI:10.1007/s40261-022-01189-9.
Background and objectives: Ropanicant hydrochloride (previously known as SUVN-911, hereinafter referred to as ropanicant) is a novel alpha4 beta2 nicotinic acetylcholine receptor (α4β2 nAchR) antagonist being developed for the treatment of major depressive disorder. The objectives of the present studies were to evaluate the safety, tolerability, and pharmacokinetics of ropanicant after single and multiple ascending doses and to evaluate the effect of food, sex, and age on its pharmacokinetics in healthy subjects. Methods: Two phase I studies have been conducted for ropanicant. Study 1 is a randomized, double-blind, placebo-controlled, first-in-human study to evaluate the safety, tolerability, and pharmacokinetics of single ascending doses (0.5, 6, 15, 30, and 60 mg) and multiple ascending doses (15, 30, and 45 mg) of ropanicant administered orally for 14 days to healthy male subjects. In Study 2, the effect of food, sex, and age on ropanicant pharmacokinetics was evaluated following a single 30-mg oral dose. Results: Ropanicant at single doses up to 60 mg and multiple doses up to 45 mg once daily was found to be safe and well tolerated in healthy subjects. The most frequently reported adverse events were headache and nausea. Ropanicant exposures were more than dose proportional following single and multiple administrations. Urinary excretion of unchanged ropanicant was low across the doses. Upon multiple dosing, 1.5- to 2.5-fold higher exposures for maximum concentration and 1.6- to 4.0-fold higher exposures for area under the concentration-time curve from time 0-24 h were observed on day 14 as compared with day 1. Sex had an effect on the pharmacokinetics of ropanicant as a 64% higher area under the concentration-time curve from time 0 to 24 h and a 26% higher maximum concentration was observed in female adults when compared with male adults. Plasma exposures were comparable in fasted versus fed conditions and in adult versus elderly subjects. Conclusions: Ropanicant was found to be safe and well tolerated following single and multiple oral administrations in healthy subjects. Ropanicant showed nonlinear pharmacokinetics and accumulation following multiple dosing. Urinary excretion represents an insignificant elimination pathway for ropanicant. Ropanicant pharmacokinetics were sex dependent, and food and age had no effect on its pharmacokinetics. Clinical trial registration: NCT03155503 and NCT03551288.
Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression
J Med Chem 2020 Mar 26;63(6):2833-2853.PMID:32026697DOI:10.1021/acs.jmedchem.9b00790.
A series of chemical optimizations guided by in vitro affinity at the α4β2 receptor in combination with selectivity against the α3β4 receptor, pharmacokinetic evaluation, and in vivo efficacy in a forced swim test resulted in identification of 3-(6-chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane hydrochloride (9h, SUVN-911) as a clinical candidate. Compound 9h is a potent α4β2 receptor ligand with a Ki value of 1.5 nM. It showed >10 μM binding affinity toward the ganglionic α3β4 receptor apart from showing selectivity over 70 other targets. It is orally bioavailable and showed good brain penetration in rats. Marked antidepressant activity and dose-dependent receptor occupancy in rats support its potential therapeutic utility in the treatment of depression. It does not affect the locomotor activity at doses several folds higher than its efficacy dose. It is devoid of cardiovascular and gastrointestinal side effects. Successful long-term safety studies in animals and phase-1 evaluation in healthy humans for safety, tolerability, and pharmacokinetics paved the way for its further development.