Ropanicant(Ropanicant) - 药物靶点：nAChRα4&β2_在研适应症：重度抑郁症，中度重度抑郁症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

nAChRα4&β2

作用机制

nAChRα4&β2拮抗剂(神经性乙酰胆碱受体蛋白α4/β2复合体拮抗剂)

治疗领域

其他疾病

在研适应症

重度抑郁症中度重度抑郁症

非在研适应症-

原研机构

Suven Life Sciences Ltd.

在研机构

Suven Life Sciences Ltd.

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C11H13ClN2O

InChIKeyPYSCVJMLJRHJGJ-OYNCUSHFSA-N

CAS号2414674-70-5

关联

3

项与 Ropanicant 相关的临床试验

NCT06126497 / Active, not recruiting临床2期

An Open-Label Study Evaluating the Safety and Efficacy of Ropanicant in Participants With Moderate to Severe Major Depressive Disorder

This is an open-label, parallel-group study to evaluate the safety and efficacy of ropanicant in participants with moderate to severe Major Depressive Disorder (MDD).

开始日期2024-02-05

申办/合作机构

Suven Life Sciences Ltd.

NCT03551288 / Completed临床1期

A Phase I, Single-Center, Single Dose Study to Evaluate the Effect of Food, Gender, and Age on Safety and Pharmacokinetic Profiles of SUVN-911 Tablets Orally Administered in Healthy Subjects

The purpose of the study is to investigate the effect of Food, Gender, and Age on the Pharmacokinetic Profile of SUVN-911 in Healthy Subjects

开始日期2018-05-22

申办/合作机构

Suven Life Sciences Ltd.

NCT03155503 / Completed临床1期

A Single-center, Double-blind, Placebo-controlled, Randomized, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SUVN-911 After Single Ascending Doses and Multiple Ascending Doses in Healthy Male Subjects

This is a Phase 1, conventional, double-blind, placebo-controlled, single-center clinical study comprised of 2 segments (Segment 1 and Segment 2) in which single and multiple doses of SUVN-911 or placebo will be orally administered to healthy male subjects to evaluate the safety, tolerability, and pharmacokinetic profile.

开始日期2017-05-22

申办/合作机构

Suven Life Sciences Ltd.

100 项与 Ropanicant 相关的临床结果

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100 项与 Ropanicant 相关的转化医学

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100 项与 Ropanicant 相关的专利（医药）

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3

项与 Ropanicant 相关的文献（医药）

2022-09-01·Clinical Drug Investigation

Safety, Tolerability, and Pharmacokinetics of Ropanicant (SUVN-911), a Novel Alpha4 Beta2 Nicotinic Acetylcholine Receptor (α4β2 nAChR) Antagonist, in Healthy Adult and Elderly Subjects

Article

作者: Shinde, Anil ; Palacharla, Veera Raghava Chowdary ; Jetta, Satish ; Ravula, Jyothsna ; Benade, Vijay ; Pandey, Santosh Kumar ; Mohammed, Abdul Rasheed ; Goyal, Vinod Kumar ; Nirogi, Ramakrishna ; Dogiparti, Dhanunjay

BACKGROUND AND OBJECTIVESRopanicant 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.METHODSTwo 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.RESULTSRopanicant 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.CONCLUSIONSRopanicant 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 REGISTRATIONNCT03155503 and NCT03551288.

2022-07-01·Psychopharmacology3区 · 医学

Ropanicant (SUVN-911), an α4β2 nicotinic acetylcholine receptor antagonist intended for the treatment of depressive disorders: pharmacological, behavioral, and neurochemical characterization

3区 · 医学

Article

作者: Abraham, Renny ; Thentu, Jagadeesh Babu ; Palacharla, Veera Raghava Chowdary ; Jayarajan, Pradeep ; Mohammed, Abdul Rasheed ; Pandey, Santosh Kumar ; Goura, Venkatesh ; Subramanian, Ramkumar ; Kallepalli, Rajesh ; Jasti, Venkat ; Petlu, Surendra ; Gagginapally, Shankar Reddy ; Medapati, Rajesh Babu ; Goyal, Vinod Kumar ; Tadiparthi, Jayaprakash ; Nirogi, Ramakrishna

RATIONALERopanicant (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.OBJECTIVESPharmacological and neurochemical characterization of Ropanicant to support a potential molecule for the treatment of depressive disorders.METHODSRopanicant 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.RESULTSRopanicant 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.CONCLUSIONSPreclinical studies with Ropanicant support the likelihood of its therapeutic utility in the treatment of depressive disorders.

2020-03-26·Journal of Medicinal Chemistry1区 · 医学

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

1区 · 医学

Article

作者: Subramanian, Ramkumar ; Shinde, Anil K. ; Bogaraju, Narsimha ; Palacharla, Raghava Choudary ; Bhyrapuneni, Gopinadh ; Jasti, Venkat ; Abraham, Renny ; Thentu, Jagadeesh Babu ; Mohammed, Abdul Rasheed ; Nirogi, Ramakrishna ; Mekala, Venkat Reddy ; Muddana, Nageswararao ; Ravella, Srinivasa Rao

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 K_i 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.

100 项与 Ropanicant 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
重度抑郁症	临床2期	美国	Suven Life Sciences Ltd.	2024-02-05
中度重度抑郁症	临床2期	美国	Suven Life Sciences Ltd.	2024-02-05

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03551288 \| NCT03155503 (Pubmed) 人工标引	临床1期	抑郁症	-	Ropanicant (Study 1, healthy male subjects)	(蓋醖製襯鹹壓淵獵觸鏇) = The most frequently reported adverse events were headache and nausea. 壓鹹顧顧糧艱觸積淵壓 (選蓋鬱餘願壓選願衊淵 )	积极	2022-08-13
				Ropanicant (Study 2)