预约演示
更新于：2025-05-16
AZD-1305
更新于：2025-05-16
概要
基本信息
药物类型 小分子化药 |
别名 AZD 1305、AZD1305 |
作用方式 阻滞剂 |
作用机制 L-type calcium channel阻滞剂(L-型电压门控性钙通道家族阻滞剂)、Nav1.5阻滞剂(V型钠通道蛋白α亚基阻滞剂)、hERG阻滞剂(电压门控性钾通道蛋白亚型Kv11.1阻滞剂) |
治疗领域 |
在研适应症- |
原研机构 |
在研机构- |
权益机构- |
最高研发阶段终止临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
登录后查看时间轴
结构/序列
分子式C22H31FN4O4 |
InChIKeyBLLNYXOLLAVTRF-UHFFFAOYSA-N |
CAS号872045-91-5 |
关联
13
项与 AZD-1305 相关的临床试验NCT00957437
A Phase I, Randomised, Open, Single-centre Study to Evaluate the Pharmacokinetics of Different Extended-release Formulations of AZD1305 When Given as Single and Repeated Oral Doses to Healthy Male Volunteers
NCT00935025
A Single-center, Single-blind, Randomized, Placebo-controlled, Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics After Single and Multiple Ascending Oral Doses of AZD1305 Extended-release Capsules in Healthy Male Japanese and Caucasian Subjects
NCT00915356
A Double-blind, Randomised, Placebo-controlled, Multicentre, Dose-escalating Study of AZD1305 Given Intravenously for Cardioversion of Atrial Fibrillation
100 项与 AZD-1305 相关的临床结果
登录后查看更多信息
100 项与 AZD-1305 相关的转化医学
登录后查看更多信息
100 项与 AZD-1305 相关的专利（医药）
登录后查看更多信息
19
项与 AZD-1305 相关的文献（医药）2024-07-01EBioMedicine
Advancing drug development for atrial fibrillation by prioritising findings from human genetic association studies
Article
作者: Providencia, Rui ; Lambiase, Pier D ; Finan, Chris ; Schilling, Richard ; Floriaan Schmidt, Amand ; Kukendrarajah, Kishore ; Farmaki, Aliki-Eleni
BACKGROUND:
Drug development for atrial fibrillation (AF) has failed to yield new approved compounds. We sought to identify and prioritise potential druggable targets with support from human genetics, by integrating the available evidence with bioinformatics sources relevant for AF drug development.
METHODS:
Genetic hits for AF and related traits were identified through structured search of MEDLINE. Genes derived from each paper were cross-referenced with the OpenTargets platform for drug interactions. Confirmation/validation was demonstrated through structured searches and review of evidence on MEDLINE and ClinialTrials.gov for each drug and its association with AF.
FINDINGS:
613 unique drugs were identified, with 21 already included in AF Guidelines. Cardiovascular drugs from classes not currently used for AF (e.g. ranolazine and carperitide) and anti-inflammatory drugs (e.g. dexamethasone and mehylprednisolone) had evidence of potential benefit. Further targets were considered druggable but remain open for drug development.
INTERPRETATION:
Our systematic approach, combining evidence from different bioinformatics platforms, identified drug repurposing opportunities and druggable targets for AF.
FUNDING:
KK is supported by Barts Charity grant G-002089 and is mentored on the AFGen 2023-24 Fellowship funded by the AFGen NIH/NHLBI grant R01HL092577. RP is supported by the UCL BHF Research Accelerator AA/18/6/34223 and NIHR grant NIHR129463. AFS is supported by the BHF grants PG/18/5033837, PG/22/10989 and UCL BHF Accelerator AA/18/6/34223 as well as the UK Research and Innovation (UKRI) under the UK government's Horizon Europe funding guarantee EP/Z000211/1 and by the UKRI-NIHR grant MR/V033867/1 for the Multimorbidity Mechanism and Therapeutics Research Collaboration. AF is supported by UCL BHF Accelerator AA/18/6/34223. CF is supported by UCL BHF Accelerator AA/18/6/34223.
2018-06-01British Journal of Pharmacology
Human hepatocytes and cytochrome P450‐selective inhibitors predict variability in human drug exposure more accurately than human recombinant P450s
Article
作者: Lundahl, Anna ; Lindmark, Bo ; Andersson, Tommy B ; Isin, Emre M ; Kanebratt, Kajsa P
Background and Purpose:
Drugs metabolically eliminated by several enzymes are less vulnerable to variable compound exposure in patients due to drug–drug interactions (DDI) or if a polymorphic enzyme is involved in their elimination. Therefore, it is vital in drug discovery to accurately and efficiently estimate and optimize the metabolic elimination profile.
Experimental Approach:
CYP3A and/or CYP2D6 substrates with well described variability in vivo in humans due to CYP3A DDI and CYP2D6 polymorphism were selected for assessment of fraction metabolized by each enzyme (fmCYP) in two in vitro systems: (i) human recombinant P450s (hrP450s) and (ii) human hepatocytes combined with selective P450 inhibitors. Increases in compound exposure in poor versus extensive CYP2D6 metabolizers and by the strong CYP3A inhibitor ketoconazole were mathematically modelled and predicted changes in exposure were compared with in vivo data.
Key Results:
Predicted changes in exposure were within twofold of reported in vivo values using fmCYP estimated in human hepatocytes and there was a strong linear correlation between predicted and observed changes in exposure (r2 = 0.83 for CYP3A, r2 = 0.82 for CYP2D6). Predictions using fmCYP in hrP450s were not as accurate (r2 = 0.55 for CYP3A, r2 = 0.20 for CYP2D6).
Conclusions and Implications:
The results suggest that variability in human drug exposure due to DDI and enzyme polymorphism can be accurately predicted using fmCYP from human hepatocytes and CYP‐selective inhibitors. This approach can be efficiently applied in drug discovery to aid optimization of candidate drugs with a favourable metabolic elimination profile and limited variability in patients.
2017-10-01British Journal of Pharmacology
Predicting QRS and PR interval prolongations in humans using nonclinical data
Article
作者: Collins, T ; Mettetal, J ; Parkinson, J ; Chappell, M J ; Bergenholm, L ; Evans, N D
Background and Purpose:
Risk of cardiac conduction slowing (QRS/PR prolongations) is assessed prior to clinical trials using in vitro and in vivo studies. Understanding the quantitative translation of these studies to the clinical situation enables improved risk assessment in the nonclinical phase.
Experimental Approach:
Four compounds that prolong QRS and/or PR (AZD1305, flecainide, quinidine and verapamil) were characterized using in vitro (sodium/calcium channels), in vivo (guinea pigs/dogs) and clinical data. Concentration‐matched translational relationships were developed based on in vitro and in vivo modelling, and the in vitro to clinical translation of AZD1305 was quantified using an in vitro model.
Key Results:
Meaningful (10%) human QRS/PR effects correlated with low levels of in vitro Nav1.5 block (3–7%) and Cav1.2 binding (13–21%) for all compounds. The in vitro model developed using AZD1305 successfully predicted QRS/PR effects for the remaining drugs. Meaningful QRS/PR changes in humans correlated with small effects in guinea pigs and dogs (QRS 2.3–4.6% and PR 2.3–10%), suggesting that worst‐case human effects can be predicted by assuming four times greater effects at the same concentration from dog/guinea pig data.
Conclusion and Implications:
Small changes in vitro and in vivo consistently translated to meaningful PR/QRS changes in humans across compounds. Assuming broad applicability of these approaches to assess cardiovascular safety risk for non–arrhythmic drugs, this study provides a means of predicting human QRS/PR effects of new drugs from effects observed in nonclinical studies.
100 项与 AZD-1305 相关的药物交易
登录后查看更多信息
研发状态
10 条进展最快的记录, 后查看更多信息
登录
| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 左心室功能不全 | 临床2期 | 瑞典 | 2008-08-01 | |
| 心房颤动 | 临床2期 | 丹麦 | 2008-03-01 | |
| 心房颤动 | 临床2期 | 挪威 | 2008-03-01 | |
| 心房颤动 | 临床2期 | 波兰 | 2008-03-01 | |
| 心房颤动 | 临床2期 | 俄罗斯 | 2008-03-01 | |
| 心房颤动 | 临床2期 | 斯洛伐克 | 2008-03-01 | |
| 心房颤动 | 临床2期 | 瑞典 | 2008-03-01 | |
| 心房扑动 | 临床2期 | 丹麦 | 2008-01-01 | |
| 心房扑动 | 临床2期 | 芬兰 | 2008-01-01 | |
| 心房扑动 | 临床2期 | 挪威 | 2008-01-01 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 228 | (AZD1305 Dose Group 1) | 膚膚獵窪艱膚憲夢膚顧(觸鬱鏇顧襯觸壓鏇繭網) = 網衊鏇衊醖淵鏇糧憲膚 構簾襯窪觸獵願遞艱鏇 (齋襯鏇鹽鹽壓衊願築構, 築憲鏇艱簾顧網繭構憲 ~ 觸淵顧蓋簾鹹齋構遞製) 更多 | - | 2012-02-01 | ||
(AZD1305 Dose Group 2) | 膚膚獵窪艱膚憲夢膚顧(觸鬱鏇顧襯觸壓鏇繭網) = 鑰鏇製鏇顧築範獵獵壓 構簾襯窪觸獵願遞艱鏇 (齋襯鏇鹽鹽壓衊願築構, 顧製選廠鬱醖鹽觸鹹簾 ~ 鹽齋鹽壓簾鹹繭願醖窪) 更多 | ||||||
临床2期 | 65 | (AZD1305 Group A and AZD1305 Group B) | 艱築繭獵製鏇鏇鏇願願(鬱廠顧鬱鹹簾鏇網餘夢) = 選廠鏇築獵獵餘艱觸鬱 獵醖網繭餘顧範蓋繭選 (鬱餘顧繭構廠餘製餘夢, 範鏇製築膚觸選鑰艱蓋 ~ 壓艱醖願醖齋鹽製艱築) 更多 | - | 2012-01-26 | ||
Placebo+AZD1305 (Placebo) | 艱築繭獵製鏇鏇鏇願願(鬱廠顧鬱鹹簾鏇網餘夢) = 醖遞蓋膚憲獵選襯遞繭 獵醖網繭餘顧範蓋繭選 (鬱餘顧繭構廠餘製餘夢, 鹽範艱觸糧築蓋觸壓網 ~ 蓋鏇選鬱艱淵鏇鹽遞餘) 更多 | ||||||
临床2期 | 171 | 願醖壓衊糧蓋簾願憲構(願廠淵蓋遞繭壓範獵願) = 築醖範醖鏇餘築顧顧蓋 夢遞繭憲願廠鹽衊簾遞 (選膚簾窪壓鏇選繭築襯 ) 更多 | 不佳 | 2011-08-01 | |||
临床2期 | 16 | (AZD1305 Dose 1 and Dose 2) | 鹹願膚構鏇蓋蓋獵鑰築(夢積衊遞願憲鬱鏇遞壓) = 觸鹽築願積憲齋鏇製蓋 鏇簾襯構蓋範顧膚構鑰 (膚顧壓鬱築醖淵淵顧糧, 鬱積網願衊遞願醖窪醖 ~ 窪膚廠繭願遞顧鑰壓築) 更多 | - | 2011-06-13 | ||
Placebo (Placebo Dose 1 and Dose 2) | 鹹願膚構鏇蓋蓋獵鑰築(夢積衊遞願憲鬱鏇遞壓) = 醖鬱鹽齋繭構鹹淵鏇膚 鏇簾襯構蓋範顧膚構鑰 (膚顧壓鬱築醖淵淵顧糧, 獵築醖衊構構壓築鹽艱 ~ 餘襯鬱鏇淵憲構淵膚網) 更多 |
登录后查看更多信息
转化医学
使用我们的转化医学数据加速您的研究。
登录
或
药物交易
使用我们的药物交易数据加速您的研究。
登录
或
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
Eureka LS:
全新生物医药AI Agent 覆盖科研全链路，让突破性发现快人一步
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。
生物序列数据库
生物药研发创新
免费使用
化学结构数据库
小分子化药研发创新
免费使用