DT-0111(DT-0111) - 药物靶点：P2RX2 x P2X3 receptor_在研适应症：咳嗽，慢性阻塞性肺疾病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

DT 0111、Aspirex

靶点

P2RX2 x P2X3 receptor

作用机制

P2RX2 antagonists(P2X2 purinoceptor antagonists)、P2X3 receptor拮抗剂(嘌呤P2X3受体拮抗剂)

治疗领域

呼吸系统疾病

在研适应症

咳嗽慢性阻塞性肺疾病

非在研适应症

慢性咳嗽

原研机构

DANMIR THERAPEUTICS LLC

在研机构

DANMIR THERAPEUTICS LLC

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C19H25N6Na4O15P3

InChIKeyOPEZBLIKWOQAOY-IVNIBNFOSA-N

CAS号2376858-68-1

关联

1

项与 DT-0111 相关的临床试验

NCT03116750 / Active, not recruitingN/A

Post-Market Clinical Follow-up Study With the ASPIREX®S Endovascular System to Assess the Safety and Effectiveness in the Treatment of DVT Patients and Special Patient Groups

The ASPIREX®S Endovascular System is a rotating and aspirating catheter system. It is intended to be used for the percutaneous transluminal removal of fresh thrombotic or thromboembolic material from native blood vessels (or vessels fitted with stents, stent grafts or native or artificial bypasses) outside the cardiopulmonary, coronary and cerebral circulations.
CAPTUREX® , a catheter with a filter basket, is intended to be used for the filtering of emboli from blood vessels during potentially embolizing procedures on the patient.
ASPIREX®S and CAPTUREX® are CE-marked (Class III) medical devices. In this study the effectiveness and safety in the removal of thrombi in veins is assessed under real life setting.

开始日期2017-04-03

申办/合作机构

Straub Medical AG

100 项与 DT-0111 相关的临床结果

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100 项与 DT-0111 相关的转化医学

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100 项与 DT-0111 相关的专利（医药）

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6

项与 DT-0111 相关的文献（医药）

2023-09-01·Purinergic signalling

DT-0111: a novel P2X3 receptor antagonist.

Article

作者: Mahadevan, Anu ; Rolland, Jean-Francois ; Pelleg, Amir ; Sirtori, Elena

Extracellular adenosine 5'-triphosphate (ATP) acts as an autocrine and paracrine agent, the actions of which on affected cells are mediated by P2 receptors (P2R), which include trans cell-membrane cationic channels (P2XRs), and G protein coupled receptors (P2YRs). The mammalian P2X receptors form homotrimeric or heterotrimeric cationic channels, each of which contains three ATP-binding sites. There are seven homotrimeric P2X receptors (P2X1-7) and three heteromeric (P2X2/P2X3, P2X4/P2X6, P2X1/P2X5). In the lungs and airways, ATP activates P2X3 and P2X2/3 receptors (P2X3R, P2X2/3R, respectively) localized on vagal sensory nerve terminals resulting in bronchoconstriction, and cough, and probably also localized release of pro-inflammatory neuropeptides via the axon reflex. Currently, several P2X3R and P2X2/3R antagonists are being developed as drug-candidates for the treatment of chronic cough. This report presents the receptor affinity data of a novel water-soluble small molecule, DT-0111, that acts as a selective P2X3R antagonist.

2019-03-01·European review for medical and pharmacological sciences

Pharmacomechanical catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis: our case series.

Article

作者: Tondi, P ; Bruni, A ; Passaro, G ; Vagnarelli, S ; Ambrogi, C ; Rabuffi, P ; Gallucci, M ; Flore, R A

OBJECTIVE:

This is a retrospective study on Pharmacomechanical Catheter-Directed Thrombolysis (PCDT) in the treatment of acute iliofemoral Deep Vein Thrombosis (DVT).

PATIENTS AND METHODS:

From March 2013 to November 2016, 22 patients (26 limbs), median age 46.7 years with acute (<21 days) extensive iliofemoral DVT underwent Percutaneous Mechanical Thrombectomy (PMT) with Aspirex (Straub Medical, Wangs, Switzerland), followed by Catheter-Directed Thrombolysis (CDT). Subsequent endovascular stenting was performed for underlying obstruction. The follow-ups were conducted up to 1 year, in two Centers by experienced operators. Post-Thrombotic Syndrome (PTS) was evaluated by assessing the Villalta Scale (VS) and measuring orthostatic venous pressure.

RESULTS:

Post-operative iliofemoral vein patency was restored in almost all cases (95.5%). Standard urokinase dose was 80.000 IU per hour; mean infusion time was 32.5 hours. Stenting was performed in 15 cases (68%). Median follow-up was 19.9 months (6-48 months); 21/22 patients completed the 12 months follow-up. At 30 days follow-up symptoms disappeared in 21/22 cases (95.5%), with one case (4.5%) of DVT recurrence. At 1-year follow-up there were 3 cases (14.2%) of mild PTS; 18 patients (85.8%) were free from PTS. At 1-year follow-up venous pressure measurement showed normal values in 11 cases (52.4%), mild hypertension in 7 patients (33.3%), moderate hypertension (80-100 mmHg) in 2 cases (9.5%) and severe hypertension (110 mmHg) in one case (4.8%). Neither major nor minor complications were observed.

CONCLUSIONS:

PMT with Aspirex combined with CDT with urokinase seems to be a safe and effective treatment for acute iliofemoral DVT and it shows promising results in reducing the risk of PTS. Thus, we suggest a controlled trial with this treatment strategy.

2019-01-01·Therapeutic advances in respiratory disease3区 · 医学

DT-0111: a novel drug-candidate for the treatment of COPD and chronic cough

3区 · 医学

ArticleOA

作者: Burnstock, Geoffrey ; Xu, Fadi ; Undem, Bradley ; Zhuang, Jianguo ; Pelleg, Amir

Background::

Extracellular adenosine 5′-triphosphate (ATP) plays important mechanistic roles in pulmonary disorders in general and chronic obstructive pulmonary disease (COPD) and cough in particular. The effects of ATP in the lungs are mediated to a large extent by P2X2/3 receptors (P2X2/3R) localized on vagal sensory nerve terminals (both C and Aδ fibers). The activation of these receptors by ATP triggers a pulmonary-pulmonary central reflex, which results in bronchoconstriction and cough, and is also proinflammatory due to the release of neuropeptides from these nerve terminals via the axon reflex. These actions of ATP in the lungs constitute a strong rationale for the development of a new class of drugs targeting P2X2/3R. DT-0111 is a novel, small, water-soluble molecule that acts as an antagonist at P2X2/3R sites.

Methods::

Experiments using receptor-binding functional assays, rat nodose ganglionic cells, perfused innervated guinea pig lung preparation ex vivo, and anesthetized and conscious guinea pigs in vivo were performed.

Results::

DT-0111 acted as a selective and effective antagonist at P2X2/3R, that is, it did not activate or block P2YR; markedly inhibited the activation by ATP of nodose pulmonary vagal afferents in vitro; and, given as an aerosol, inhibited aerosolized ATP-induced bronchoconstriction and cough in vivo.

Conclusions::

These results indicate that DT-0111 is an attractive drug-candidate for the treatment of COPD and chronic cough, both of which still constitute major unmet clinical needs. The reviews of this paper are available via the supplementary material section.

100 项与 DT-0111 相关的药物交易

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