NTP-42(NTP-42) - 药物靶点：TBXA2R_在研适应症：肺动脉高压，心脏衰竭，肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

NTP42:KVA4

靶点

TBXA2R

作用机制

TBXA2R拮抗剂(血栓素A2受体拮抗剂)

治疗领域

呼吸系统疾病其他疾病肿瘤+ [2]

在研适应症

肺动脉高压心脏衰竭肿瘤+ [2]

非在研适应症-

原研机构

Atxa Therapeutics Ltd.初创企业

在研机构

Atxa Therapeutics Ltd.初创企业

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C25H23F2N3O5S

InChIKeyRIIKDGPBTPECSW-UHFFFAOYSA-N

CAS号2055599-51-2

关联

2

项与 NTP-42 相关的临床试验

NCT06092788 / Completed临床1期

Phase 1, Randomised, Open-label, 3-way Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetics (With Food Effect), and Relative Bioavailability of NTP42:KVA4 Given as a Capsule, Compared With a Liquid, in Healthy Volunteers

This Phase 1 clinical trial will assess the safety, tolerability and pharmacokinetics (PK) of a solid capsule form of NTP42:KVA4 in male and female healthy volunteers. In a randomised, 3-way cross-over study, the Trial will involve 3 dose sessions where all volunteers will receive 3 single doses of NTP42:KVA4. In two of the dose sessions, volunteers will be fasted where, in one, they will be given the NTP42:KVA4 capsule and, in another, they will be given NTP42:KVA4 in oral liquid form. To test the effect of food on drug absorption (PK), the volunteers will also be given the NTP42:KVA4 capsule after eating a full breakfast.

开始日期2023-11-24

申办/合作机构

Atxa Therapeutics Ltd.初创企业

[+1]

NCT04919863 / Completed临床1期

A Phase I Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of NTP42:KVA4 in Healthy Volunteers

A Phase I clinical trial to assess the safety, tolerability, and pharmacokinetics of NTP42:KVA4 following oral administration in a randomized, double-blind, placebo-controlled trial. The trial will involve of 2 phases, a single ascending dose (SAD) phase and a multiple ascending dose (MAD) phase. The SAD phase will incorporate a food effect arm.

开始日期2021-05-24

申办/合作机构

Atxa Therapeutics Ltd.初创企业

[+1]

100 项与 NTP-42 相关的临床结果

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100 项与 NTP-42 相关的转化医学

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100 项与 NTP-42 相关的专利（医药）

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4

项与 NTP-42 相关的文献（医药）

2020-12-01·European Journal of Pharmacology3区 · 医学

Efficacy of the thromboxane receptor antagonist NTP42 alone, or in combination with sildenafil, in the sugen/hypoxia-induced model of pulmonary arterial hypertension

3区 · 医学

Article

作者: Adão, Rui ; Reid, Helen M ; Kinsella, B Therese ; Mendes-Ferreira, Pedro ; Bialesova, Lucia ; Mulvaney, Eamon P ; Brás-Silva, Carmen

NTP42 is a novel antagonist of the thromboxane A₂ receptor (TP) in development for the treatment of pulmonary arterial hypertension (PAH). Recent studies demonstrated that NTP42 and TP antagonism have a role in alleviating PAH pathophysiology. However, the efficacy of NTP42 when used in combination with existing PAH therapies has not yet been investigated. Herein, the Sugen 5416/hypoxia (SuHx)-induced PAH model was employed to evaluate the efficacy of NTP42 when used alone or in dual-therapy with Sildenafil, a PAH standard-of-care. PAH was induced in rats by injection of Sugen 5416 and exposure to hypoxia for 21 days. Thereafter, animals were treated orally twice-daily for 28 days with either vehicle, NTP42 (0.05 mg/kg), Sildenafil (50 mg/kg), or NTP42+Sildenafil (0.05 mg/kg + 50 mg/kg, respectively). While Sildenafil or NTP42 mono-therapy led to non-significant reductions in the SuHx-induced rises in mean pulmonary arterial pressure (mPAP) or right ventricular systolic pressure (RSVP), combined use of NTP42+Sildenafil significantly reduced these increases in mPAP and RVSP. Detailed histologic analyses of pulmonary vessel remodelling, right ventricular hypertrophy and fibrosis demonstrated that while NTP42 and Sildenafil in mono-therapy resulted in significant benefits, NTP42+Sildenafil in dual-therapy showed an even greater benefit over either drug used alone. In summary, combined use of NTP42+Sildenafil in dual-therapy confers an even greater benefit in treating or offsetting key aetiologies underlying PAH. These findings corroborate earlier preclinical findings suggesting that, through antagonism of TP signalling, NTP42 attenuates PAH pathophysiology, positioning it as a novel therapeutic for use alone or in combination therapy regimens.

2020-12-01·BMC Pulmonary Medicine

NTP42, a novel antagonist of the thromboxane receptor, attenuates experimentally induced pulmonary arterial hypertension

Article

作者: Bouchard, Annie ; Salvail, Dany ; Reid, Helen M ; Bialesova, Lucia ; Mulvaney, Eamon P ; Kinsella, B Therese

AbstractBackgroundNTP42is a novel antagonist of the thromboxane prostanoid receptor (TP), currently in development for the treatment of pulmonary arterial hypertension (PAH). PAH is a devastating disease with multiple pathophysiological hallmarks including excessive pulmonary vasoconstriction, vascular remodelling, inflammation, fibrosis, in situ thrombosis and right ventricular hypertrophy. Signalling through the TP, thromboxane (TX) A2is a potent vasoconstrictor and mediator of platelet aggregation. It is also a pro-mitogenic, pro-inflammatory and pro-fibrotic agent. Moreover, the TP also mediates the adverse actions of the isoprostane 8-iso-prostaglandin F2α, a free-radical-derived product of arachidonic acid produced in abundance during oxidative injury. Mechanistically, TP antagonists should treat most of the hallmarks of PAH, including inhibiting the excessive vasoconstriction and pulmonary artery remodelling, in situ thrombosis, inflammation and fibrosis. This study aimed to investigate the efficacy ofNTP42in the monocrotaline (MCT)-induced PAH rat model, alongside current standard-of-care drugs.MethodsPAH was induced by subcutaneous injection of 60 mg/kg MCT in male Wistar–Kyoto rats. Animals were assigned into groups: 1. ‘No MCT’; 2. ‘MCT Only’; 3. MCT + NTP42(0.25 mg/kg BID); 4. MCT + Sildenafil (50 mg/kg BID), and 5. MCT + Selexipag (1 mg/kg BID), where 28-day drug treatment was initiated within 24 h post-MCT.ResultsFrom haemodynamic assessments, NTP42reduced the MCT-induced PAH, including mean pulmonary arterial pressure (mPAP) and right systolic ventricular pressure (RSVP), being at least comparable to the standard-of-care drugs Sildenafil or Selexipag in bringing about these effects. Moreover,NTP42was superior to Sildenafil and Selexipag in significantly reducing pulmonary vascular remodelling, inflammatory mast cell infiltration and fibrosis in MCT-treated animals.ConclusionsThese findings suggest thatNTP42and antagonism of the TP signalling pathway have a relevant role in alleviating the pathophysiology of PAH, representing a novel therapeutic target with marked benefits over existing standard-of-care therapies.

Frontiers in Pharmacology

Evaluation of NTP42, a novel thromboxane receptor antagonist, in a first-in-human phase I clinical trial

Article

作者: Boyce, Malcolm ; Mulvaney, Eamon P ; Reid, Helen M ; Kinsella, B Therese ; Maginn, Mark ; Yamamoto, Takahiro ; Perkins, C Michael

Background: The thromboxane receptor (TP) antagonist NTP42 is in clinical development for treatment of cardiopulmonary diseases, such as pulmonary arterial hypertension. In this randomized, placebo-controlled Phase I clinical trial, NTP42, administered as the oral formulation NTP42:KVA4, was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in healthy males.Methods: The first-in-human trial had three Parts: A, single ascending dose (SAD) study with seven groups given 0.25–243 mg NTP42:KVA4 or placebo; B, food effect study where one SAD group (9 mg) was also given NTP42:KVA4 or placebo after a high-fat breakfast; C, multiple ascending dose study with three groups given 15–135 mg NTP42:KVA4 or placebo once-daily for 7 days.Results: Seventy-nine volunteers participated. No serious adverse events occurred, where any drug- or placebo-related adverse events were mild to moderate, with no correlation to NTP42:KVA4 dose. NTP42 was rapidly absorbed, yielding dose proportional increases in exposure after single and repeat dosing. PK confirmed that, with a clearance (T1/2) of 18.7 h, NTP42:KVA4 is suited to once-daily dosing, can be taken with or without food, and does not accumulate on repeat dosing. At doses ≥1 mg, NTP42 led to complete and sustained inhibition of thromboxane-, but not ADP-, induced platelet aggregation ex vivo, with direct correlation between NTP42 exposure and duration of PD effects.Conclusion: Orally administered NTP42:KVA4 was well tolerated, with favorable PK/PD profiles and evidence of specific TP target engagement. These findings support continued clinical development of NTP42:KVA4 for cardiopulmonary or other relevant diseases with unmet needs.Clinical Trial Registration:clinicaltrials.gov, identifier NCT04919863.

100 项与 NTP-42 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
肺动脉高压	临床2期	爱尔兰	Atxa Therapeutics Ltd.初创企业	2022-01-30
心脏衰竭	临床前	爱尔兰	Atxa Therapeutics Ltd.初创企业	2022-01-30
肿瘤	临床前	爱尔兰	Atxa Therapeutics Ltd.初创企业	2022-01-30
肺心病	临床前	爱尔兰	Atxa Therapeutics Ltd.初创企业	2022-01-30
泌尿生殖系统疾病	药物发现	爱尔兰	Atxa Therapeutics Ltd.初创企业	2022-01-30