Zamicastat(Zamicastat) - 药物靶点：DBH_专利_临床

概要

基本信息

药物类型

小分子化药

别名

BIA-5-1058

靶点

DBH

作用机制

DBH抑制剂(多巴胺β-羟化酶抑制剂)

治疗领域

呼吸系统疾病其他疾病心血管疾病

在研适应症-

非在研适应症

慢性心力衰竭心脏衰竭高血压+ [1]

原研机构

BIAL-Portela & Cia SA

在研机构-

非在研机构

BIAL-Portela & Cia SA

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)-

特殊审评孤儿药 (美国)

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结构

分子式C21H21F2N3OS

InChIKeyZSSLCFLHEFXANG-GOSISDBHSA-N

CAS号1080028-80-3

关联

18

项与 Zamicastat 相关的临床试验

EUCTR2018-002796-18-IT / Not yet recruiting临床2期

An open-label, multicentre study to evaluate the safety and efficacy of zamicastat as adjunctive therapy in long-term treatment of pulmonary arterial hypertension (PAH) disease - Safety and efficacy of BIA 5-1058 in PAH

开始日期2019-11-28

申办/合作机构

BIAL-Portela & Cia SA

NCT06009185 / Completed临床2期

An Open-label, Multicentre Study to Evaluate the Safety and Efficacy of Zamicastat as Adjunctive Therapy in Long-term Treatment of Pulmonary Arterial Hypertension (PAH) Disease

This study aims to assess the safety and tolerability of the individual highest tolerated zamicastat doses, achieved in the study BIA-51058-201, during long-term treatment in Pulmonary Arterial Hypertension (PAH) disease.

开始日期2019-06-26

申办/合作机构

BIAL-Portela & Cia SA

NCT04316143 / Completed临床2期

An Open-label, Multicentre Study to Evaluate Pharmacokinetics, Safety and Efficacy of Zamicastat as Adjunctive Therapy in Pulmonary Arterial Hypertension (PAH)

This Study evaluates the pharmacokinetic (PK) profile of different zamicastat doses in Pulmonary arterial hypertension (PAH) patients to find the most promising therapeutic dosage range for the treatment of PAH disease

开始日期2019-06-03

申办/合作机构

BIAL-Portela & Cia SA

100 项与 Zamicastat 相关的临床结果

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100 项与 Zamicastat 相关的转化医学

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100 项与 Zamicastat 相关的专利（医药）

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7

项与 Zamicastat 相关的文献（医药）

2024-11-01·JOURNAL OF CLINICAL PHARMACOLOGY

Drug‐Drug Interaction between Oral Zamicastat and Continuous Epoprostenol Infusion at Steady‐State Conditions in Healthy Subjects

Article

作者: Henriques, Sara Carolina ; Magalhães, Luís ; Soares‐da‐Silva, Patrício ; Gama, Helena ; Silva, Nuno ; Almeida, Luis ; Fonseca, Marlene ; Guimarães, Andreia

Abstract:

This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single‐center, open‐label, two‐period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8‐day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat‐to‐epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for Cav,ss and area under the plasma concentration–time curve from time 0 up to 16 h at steady state (AUC0‐16,ss) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%‐125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC0‐τ,ss, the zamicastat plus epoprostenol‐to‐zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat Cmax,ss, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, Cmax,ss and AUC0‐τ,ss and the zamicastat plus epoprostenol‐to‐zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for Cmax,ss and between 21% and 41% for AUC0‐τ,ss, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant.

2024-11-01·BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Effect of zamicastat on blood pressure and heart rate response to cold pressor test: A double‐blind, randomized, placebo‐controlled study in healthy subjects

Article

作者: Magalhães, Luís ; Henriques, Sara Carolina ; Silva, Nuno ; Almeida, Luís ; Gama, Helena ; Soares‐da‐Silva, Patrício ; Pinto, Filipe ; Fonseca, Marlene ; Ribeiro, Cheila ; Castilla‐Fernández, Guillermo

Abstract:

Aims:

Dopamine beta‐hydroxylase (DβH) inhibitors, like zamicastat, hold promise for treating pulmonary arterial hypertension. This study aimed to validate the mechanism of action of zamicastat by studying its effect on the overdrive of the sympathetic nervous system (SNS).

Methods:

A single‐centre, prospective, double‐blind, randomized, placebo‐controlled, crossover study evaluated the effect of 400 mg zamicastat in 22 healthy male subjects. Cold pressor test (CPT) was performed at screening and each treatment period on Days −1 and 10. Plasma and 24 h‐urine levels of dopamine (DA), epinephrine (EPI) and norepinephrine (NE), and plasma DβH activity, were measured.

Results:

Compared to placebo, zamicastat showed a − 4.62 mmHg decrease in systolic blood pressure during the cold stimulus vs. rest phases on Day 10 of CPT (P = .020). Zamicastat decreased mean arterial pressure response to cold stimulus during CPT (−2.62 mmHg; P = .025). At Day 10, zamicastat significantly increased plasma DA, before CPT (12.63 ng/L; P = .040) and after CPT (19.22 ng/L; P = .001) as well as the estimated plasma EPI change from baseline after CPT (P = .040). Inhibition of plasma DβH activity ranged from 19.8% to 25.0%. At Day 10, significant reductions in 24‐h urinary excretion of EPI (P = .002) and NE (P = .001) were observed. Zamicastat Cτ geometric mean ± GSD ranged from 45.86 ± 1.46 ng/mL on Day 3 to 58.64 ± 1.52 ng/mL on Day 10, with moderate inter‐individual variability (CV: 32.6%–36.6%). Steady state was already achieved on Day 6.

Conclusions:

Our results demonstrated the effect of zamicastat on the overdrive sympathetic response to cold stimulus, confirming its potential as SNS modulator.

2020-09-01·Expert opinion on investigational drugs2区 · 医学

Dopamine β hydroxylase as a potential drug target to combat hypertension

2区 · 医学

Review

作者: Prabhakar, Pankaj ; Kundu, Suman ; Saini, Manisha ; Dey, Sanjay Kumar

INTRODUCTION:

Despite a large number of commercially available drugs, hypertension and related cardiovascular diseases remain a global problem. It is thus imperative that novel drugs and therapeutic strategies are regularly identified, and alternative targets explored. Dopamine β hydroxylase (DBH), a key player in the catecholamine biosynthetic pathway, may provide a therapeutic opportunity and should be extensively explored as a target for potent anti-hypertensives. Inhibitors of DBH have been successful in combating hypertension, as evidenced by the outcome of clinical trials for etamicastat and zamicastat.

AREAS COVERED:

We shed light on the strategies employed to identify inhibitors of the enzyme and outline the advantages that the target might offer. Structural and functional details of the enzyme are described along with specific methodologies for drug discovery that were never utilized for the therapeutic target.

EXPERT OPINION:

Effective inhibitors of the enzyme may be identified with computer-aided structure-based design. Adoption of new methodologies and the assessment of newly designed inhibitors in DBH-specific animal models will provide new, safe, and cost-effective therapeutic opportunities.

1

项与 Zamicastat 相关的新闻（医药）

2021-08-25

·GlobeNewswire

Pulmonary Arterial Hypertension Pipeline Insight Research

Los Angeles, USA, Aug. 24, 2021 (GLOBE NEWSWIRE) -- Pulmonary Arterial Hypertension Pipeline Insight Research Report Around 55+ key companies are developing therapies for Pulmonary Arterial Hypertension, among which the drug of Liquidia Technologies is in the advanced stage (Pre Registration) DelveInsight’s “Pulmonary Arterial Hypertension (PAH) Pipeline Insight” report provides comprehensive insights about 55+ companies and 55+ pipeline drugs in the Pulmonary Arterial Hypertension pipeline landscapes. It comprises Pulmonary Arterial Hypertension pipeline drug profiles, including clinical and non-clinical stage products. It also includes the Pulmonary Arterial Hypertension therapeutics assessment by product type, stage, route of administration, and molecule type and further highlights the inactive Pulmonary Arterial Hypertension pipeline products. Some of the key takeaways from the Pulmonary Arterial Hypertension Pipeline Report Get an overview of pipeline landscape @ Pulmonary Arterial Hypertension Clinical Trials Analysis Pulmonary Arterial Hypertension (PAH) is a rare, progressive disorder characterized by high blood pressure in the arteries of the lungs for no apparent reason. Pulmonary Arterial Hypertension Emerging Drugs Sotatercept is a first-in-class therapeutic fusion protein composed of the extracellular domain of human activin receptor type IIA, fused to the Fc domain of human immunoglobulin G1 (IgG1). The United States Food and Drug Administration (FDA) has granted Orphan Drug designation and Breakthrough Therapy designation to sotatercept for the treatment of PAH; the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to sotatercept for the treatment of PAH. Sotatercept is in Phase III clinical trials for the treatment of PAH. LIQ861 is an investigational, inhaled dry powder formulation of treprostinil designed using the Company’s novel PRINT technology and engineered to enhance deep-lung delivery of treprostinil in PAH patients using a convenient, palm-sized dry powder inhaler. Liquidia resubmits New Drug Application for LIQ861 under the 505(b)(2) regulatory pathway for the treatment of pulmonary arterial hypertension (PAH). Gossamer Bio is developing Seralutinib (GB002) for the treatment of Pulmonary Arterial Hypertension. It is currently in the Phase II stage of development (NCT04456998). It acts as an inhibitor of Platelet-derived growth factor receptors, CSF1R, c-KIT. Bial is developing Zamicastat for the treatment of Pulmonary Arterial Hypertension. It is currently in the Phase II stage of development (NCT04316143). It acts as an inhibitor of Dopamine beta-hydroxylase. For further information, refer to the detailed report @ Pulmonary Arterial Hypertension Pipeline Therapeutics Scope of Pulmonary Arterial Hypertension Pipeline Drug Insight · Pulmonary Arterial Hypertension Therapies Late-stage (Phase III) · Pulmonary Arterial Hypertension Therapies Mid-stage (Phase II)· Pulmonary Arterial Hypertension Therapies Early-stage (Phase I) · Pulmonary Arterial Hypertension Preclinical stage and Discovery candidates · Discontinued and Inactive candidates · Epoprostenol receptor agonists· Activin inhibitors· Platelet-derived growth factor receptor antagonists· Dopamine beta-hydroxylase inhibitors· Vasoactive intestinal peptide type II receptor agonists· Angiogenesis inhibitors; Bcr-abl tyrosine kinase inhibitors · Cyclin-dependent kinase 4 inhibitors; Cyclin-dependent kinase 6 inhibitors· Galectin 3 inhibitors · Peptides· Monoclonal antibodies· Small molecules · Proteins· Gene therapy · Parenteral · Oral· Intravenous· Subcutaneous · Monotherapy· Combination· Mono/Combination Key Questions regarding Current Pulmonary Arterial Hypertension Treatment Landscape and Emerging Therapies Answered in the Pipeline Report Table of Contents Get a customized pipeline report @ Pulmonary Arterial Hypertension Drugs Pipeline Report Other Reports About DelveInsightDelveInsight is a leading Business Consultant, and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. It also provides Healthcare Consulting services comprising credible market analysis that will help accelerate the business growth and overcome challenges with a practical approach.

基因疗法抗体孤儿药突破性疗法First in Class

100 项与 Zamicastat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12389

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
肺动脉高压	临床2期	奥地利	BIAL-Portela & Cia SA	2019-06-03
肺动脉高压	临床2期	德国	BIAL-Portela & Cia SA	2019-06-03
肺动脉高压	临床2期	意大利	BIAL-Portela & Cia SA	2019-06-03
肺动脉高压	临床2期	葡萄牙	BIAL-Portela & Cia SA	2019-06-03
肺动脉高压	临床2期	西班牙	BIAL-Portela & Cia SA	2019-06-03
肺动脉高压	临床2期	乌克兰	BIAL-Portela & Cia SA	2019-06-03
肺动脉高压	临床2期	英国	BIAL-Portela & Cia SA	2019-06-03
心脏衰竭	临床1期	英国	BIAL-Portela & Cia SA	2018-04-09
慢性心力衰竭	临床1期	荷兰	BIAL-Portela & Cia SA	2011-03-01
高血压	临床1期	荷兰	BIAL-Portela & Cia SA	2011-03-01

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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


NCT04316143 (CTgov)	临床2期	肺动脉高压	33	Oral zamicastat (50 mg Zamicastat)	醖構膚壓鑰襯蓋蓋蓋餘(襯製糧艱顧鬱餘獵齋憲) = 選醖鏇獵膚憲夢選餘襯築襯觸窪淵顧襯構衊夢 (鏇選構糧膚遞蓋範膚膚, 範築築齋壓製範鹹淵糧 ~ 鹽壓積觸製簾網糧鑰簾) 更多	-	2024-10-15
				Oral zamicastat (100 mg Zamicastat Once Daily)	醖構膚壓鑰襯蓋蓋蓋餘(襯製糧艱顧鬱餘獵齋憲) = 壓齋範築構選鏇艱襯顧築襯觸窪淵顧襯構衊夢 (鏇選構糧膚遞蓋範膚膚, 艱鹹壓餘顧醖觸鬱夢顧 ~ 廠夢襯築觸鑰積齋衊願) 更多
BIA-51058-111 (ERS2021)	N/A	-	44	Zamicastat 400 mg	製鏇蓋鹽願淵膚鑰鹹願(鏇獵醖繭廠遞觸廠糧製) = 壓膚鬱鹹獵鏇淵築築觸網鏇餘醖壓獵製憲範鹽 (鬱鑰範顧願衊衊蓋繭構, 94 ~ 108) 更多	-	2021-09-05
				Furosemide 40 mg	製鏇蓋鹽願淵膚鑰鹹願(鏇獵醖繭廠遞觸廠糧製) = 憲襯鹽艱蓋廠膚鑰膚遞網鏇餘醖壓獵製憲範鹽 (鬱鑰範顧願衊衊蓋繭構, 64 ~ 87) 更多
ERS2020	N/A	-	20	Zamicastat 400 mg	顧範餘廠餘醖鹽鑰積構(憲衊積網顧構願窪廠鹹) = 製構鹽餘範鹽衊網鹹蓋鬱觸選遞簾廠積壓範鏇 (獵鹽壓鑰蓋鹹蓋顧鏇觸, 79 ~ 111) 更多	-	2020-09-07
				Sildenafil 20 mg	顧範餘廠餘醖鹽鑰積構(憲衊積網顧構願窪廠鹹) = 獵蓋蓋膚醖築憲憲鬱齋鬱觸選遞簾廠積壓範鏇 (獵鹽壓鑰蓋鹹蓋顧鏇觸, 89 ~ 107) 更多