更新于：2024-12-21
Sembragiline
更新于：2024-12-21
概要
基本信息
在研机构- |
最高研发阶段无进展临床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C19H19FN2O3 |
InChIKeyVMAVCCUQTALHOB-INIZCTEOSA-N |
CAS号676479-06-4 |
关联
9
项与 Sembragiline 相关的临床试验A multi center, open label study to assess the inhibiton of Brain MAO-B by RG1577 after repeated dosing in Japanese patients with Alzheimers Disease using positron emission tomography (PET)
A 2 PART STUDY IN HEALTHY SUBJECTS: PART A: A MULTIPLE DOSE, RANDOMIZED, PLACEBO CONTROLLED STUDY TO EVALUATE THE SAFETY AND TOLERABILITY OF SUPRA-THERAPEUTIC DOSES OF RO4602522; PART B: A MULTIPLE-DOSE, RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, PLACEBO CONTROLLED, POSITIVE-CONTROL, PARALLEL GROUP STUDY TO INVESTIGATE THE EFFECT OF RO4602522 ON THE QTC INTERVAL
A multi center, open label study to assess the inhibiton of Brain MAO-B by RG1577 after repeated dosing in Japanese patients with Alzheimers Disease using positron emission tomography (PET)
100 项与 Sembragiline 相关的临床结果
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100 项与 Sembragiline 相关的转化医学
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100 项与 Sembragiline 相关的专利（医药）
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5
项与 Sembragiline 相关的文献（医药）2018-01-01Bioorganic & medicinal chemistry3区 · 医学
Synthesis and evaluation of biaryl derivatives for structural characterization of selective monoamine oxidase B inhibitors toward Parkinson’s disease therapy
3区 · 医学
Article
作者: Ki Duk Park ; Gyoonhee Han ; Su Jeong Shin ; Ji Won Choi ; Yong Sun Bahn ; Seul Ki Yeon ; Hyeon Jeong Kim ; Jong Hyun Park ; Siwon Kim ; Yong Sup Lee ; Ye Rim Lee ; Ae Nim Pae ; Bo Ko Jang
Benzyloxyphenyl moiety is a common structure of highly potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B), safinamide and sembragiline. We synthesized 4-(benzyloxy)phenyl and biphenyl-4-yl derivatives including halogen substituents on the terminal aryl unit. In addition, we modified the carbon linker between amine group and the biaryl linked unit. Among synthesized compounds, 12c exhibited the most potent and selective MAO-B inhibitory effect (hMAO-B IC50: 8.9 nM; >10,000-fold selectivity over MAO-A) as a competitive inhibitor. In addition, 12c showed greater MAO-B inhibitory activity and selectivity compared to well-known MAO-B inhibitors such as selegiline, safinamide and sembragiline. In the MPTP-induced mouse model of Parkinson's disease (PD), 12c significantly protected the tyrosine hydroxylase (TH)-immunopositive DAergic neurons and attenuated the PD-associated behavioral deficits. This study suggests characteristic structures as a MAO-B inhibitor that may provide a good insight for the development of therapeutic agents for PD.
2017-06-23Journal of Alzheimer's disease : JAD3区 · 医学
Sembragiline in Moderate Alzheimer’s Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD)
3区 · 医学
Article
作者: Ricci, Benedicte ; Muelhardt, Nicoletta Milani ; Santarelli, Luca ; Savola, Juha-Matti ; Carey, Tracie ; Boada, Merce ; Doody, Rachelle S. ; Fontoura, Paulo ; Lanctot, Krista ; Borroni, Edilio ; Gilaberte, Inma ; Mannino, Marie ; Nave, Stephane ; Nikolcheva, Tania ; Czech, Christian ; Ostrowitzki, Susanne ; Gerlach, Irene ; Pauly-Evers, Meike ; Dukart, Juergen ; Grimmer, Timo ; Delmar, Paul ; Moran, Emma
BACKGROUND:
Sembragiline is a potent, selective, long-acting, and reversible MAO-B inhibitor developed as a potential treatment for Alzheimer's disease (AD).
OBJECTIVE:
To evaluate the safety, tolerability, and efficacy of sembragiline in patients with moderate AD.
METHODS:
In this Phase II study (NCT01677754), 542 patients with moderate dementia (MMSE 13-20) on background acetylcholinesterase inhibitors with/without memantine were randomized (1:1:1) to sembragiline 1 mg, 5 mg, or placebo once daily orally for 52 weeks.
RESULTS:
No differences between treated groups and placebo in adverse events or in study completion. The primary endpoint, change from baseline in ADAS-Cog11, was not met. At Week 52, the difference between sembragiline and placebo in ADAS-Cog11 change from baseline was - 0.15 (p = 0.865) and 0.90 (p = 0.312) for 1 and 5 mg groups, respectively. Relative to placebo at Week 52 (but not at prior assessment times), the 1 mg and 5 mg sembragiline groups showed differences in ADCS-ADL of 2.64 (p = 0.051) and 1.89 (p = 0.160), respectively. A treatment effect in neuropsychiatric symptoms (as assessed by the difference between sembragiline and placebo on BEHAVE-AD-FW) was also seen at Week 52 only: - 2.80 (p = 0.014; 1 mg) and - 2.64 (p = 0.019; 5 mg), respectively. A post hoc subgroup analysis revealed greater treatment effects on behavior and functioning in patients with more severe baseline behavioral symptoms (above the median).
CONCLUSIONS:
This study showed that sembragiline was well-tolerated in patients with moderate AD. The study missed its primary and secondary endpoints. Post hoc analyses suggested potential effect on neuropsychiatric symptoms and functioning in more behaviorally impaired study population at baseline.
2017-03-01European Journal of Nuclear Medicine and Molecular Imaging
Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer’s disease and elderly controls after oral administration of sembragiline
Article
作者: Stenkrona, Per ; Al-Tawil, Nabil ; Forsberg, Anton ; Sturm, Stefan ; Ejduk, Zbigniew ; Andreasen, Niels ; Nave, Stephane ; Seneca, Nicholas ; Nakao, Ryuji ; Halldin, Christer ; Ricci, Benedicte ; Jamois, Candice ; Fazio, Patrik ; Comley, Robert A ; Varrone, Andrea ; Akenine, Ulrika
PURPOSE:
In Alzheimer's disease (AD), increased metabolism of monoamines by monoamine oxidase type B (MAO-B) leads to the production of toxic reactive oxygen species (ROS), which are thought to contribute to disease pathogenesis. Inhibition of the MAO-B enzyme may restore brain levels of monoaminergic neurotransmitters, reduce the formation of toxic ROS and reduce neuroinflammation (reactive astrocytosis), potentially leading to neuroprotection. Sembragiline (also referred as RO4602522, RG1577 and EVT 302 in previous communications) is a potent, selective and reversible inhibitor of MAO-B developed as a potential treatment for AD.
METHODS:
This study assessed the relationship between plasma concentration of sembragiline and brain MAO-B inhibition in patients with AD and in healthy elderly control (EC) subjects. Positron emission tomography (PET) scans using [11C]-L-deprenyl-D2 radiotracer were performed in ten patients with AD and six EC subjects, who received sembragiline each day for 6-15 days.
RESULTS:
At steady state, the relationship between sembragiline plasma concentration and MAO-B inhibition resulted in an Emax of ∼80-90 % across brain regions of interest and in an EC50 of 1-2 ng/mL. Data in patients with AD and EC subjects showed that near-maximal inhibition of brain MAO-B was achieved with 1 mg sembragiline daily, regardless of the population, whereas lower doses resulted in lower and variable brain MAO-B inhibition.
CONCLUSIONS:
This PET study confirmed that daily treatment of at least 1 mg sembragiline resulted in near-maximal inhibition of brain MAO-B enzyme in patients with AD.
100 项与 Sembragiline 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D11224 | - | - | - |
研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 阿尔茨海默症 | 临床2期 | 美国 | 2012-10-24 | |
| 阿尔茨海默症 | 临床2期 | 澳大利亚 | 2012-10-24 | |
| 阿尔茨海默症 | 临床2期 | 加拿大 | 2012-10-24 | |
| 阿尔茨海默症 | 临床2期 | 捷克 | 2012-10-24 | |
| 阿尔茨海默症 | 临床2期 | 法国 | 2012-10-24 | |
| 阿尔茨海默症 | 临床2期 | 德国 | 2012-10-24 | |
| 阿尔茨海默症 | 临床2期 | 意大利 | 2012-10-24 | |
| 阿尔茨海默症 | 临床2期 | 波兰 | 2012-10-24 | |
| 阿尔茨海默症 | 临床2期 | 韩国 | 2012-10-24 | |
| 阿尔茨海默症 | 临床2期 | 西班牙 | 2012-10-24 |
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