DNK-333(DNK-333) - 药物靶点：NK1R x NK2R_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

NK1R x NK2R

作用机制

NK1R 拮抗剂(神经激肽-1-受体拮抗剂)、NK2R拮抗剂(神经激肽-2-受体拮抗剂)

治疗领域

免疫系统疾病遗传病与畸形消化系统疾病+ [2]

在研适应症-

非在研适应症

咳嗽特应性皮炎腹泻型肠易激综合征+ [1]

原研机构

Novartis Pharma AG

在研机构-

非在研机构

Novartis AG

Novartis Pharmaceuticals Corp.

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C27H25Cl2F6N3O3

InChIKeyBHCJHYIMNHXLOM-SIKLNZKXSA-N

CAS号203932-02-9

关联

4

项与 DNK-333 相关的临床试验

NCT01033097 / Completed临床2期

A Multicenter, Randomized, Double-blinded, Placebo and Positive Controlled Study to Evaluate the Anti-pruritic Effect, Safety and Tolerability, Systemic and Skin Exposure, After 2 Weeks of Treatment With a Microemulsion Formulation of DNK333 in Atopic Dermatitis Patients

This study will assess the safety and efficacy of DNK333 in patients with atopic dermatitis suffering from pruritus, who require systemic treatment of the disease.

开始日期2009-11-01

申办/合作机构

Novartis Pharmaceuticals Corp.

NCT00394173 / Completed临床2期

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of DNK333 25mg b.i.d. Given Orally for 4 Weeks in Female Patients With Diarrhea-predominant Irritable Bowel Syndrome (IBS-D)

The purpose of this study is to evaluate the efficacy of DNK333 compared to placebo for relieving symptoms of IBS-D in female patients.

开始日期2006-09-01

申办/合作机构

Novartis AG

NCT00699166 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled, Multicenter 2-Week Pilot Study to Evaluate the Efficacy, Safety and Tolerability of DNK333 (25 and 100 mg Bid) Given Orally in Female Patients With Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)

This study will evaluate the tolerability, safety and efficacy of DNK333 against diarrhea caused by Irritable Bowel Syndrome in women.

开始日期2004-04-01

申办/合作机构

Novartis AG

100 项与 DNK-333 相关的临床结果

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100 项与 DNK-333 相关的转化医学

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100 项与 DNK-333 相关的专利（医药）

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9

项与 DNK-333 相关的文献（医药）

2011-06-01·Alimentary Pharmacology & Therapeutics1区 · 医学

Randomised clinical trial: the clinical effects of a novel neurokinin receptor antagonist, DNK333, in women with diarrhoea-predominant irritable bowel syndrome

1区 · 医学

Article

作者: G. Barton ; E. Weber ; S. Zakko ; C. Dunger-Baldauf ; A. Rühl

BACKGROUNDNeurokinin receptors may play an important role in the visceral hypersensitivity and exaggerated motor/secretory activity associated with diarrhoea-predominant irritable bowel syndrome (IBS-D).AIMTo evaluate the effects of DNK333, a novel neurokinin antagonist, in women with IBS-D.METHODSIn two consecutive phase II studies, women with IBS-D were randomised to twice-daily (b.d.) DNK333 25 mg, DNK333 100 mg or placebo for 2 weeks (Trial 1), or DNK333 25 mg b.d. or placebo for 4 weeks (Trial 2). Primary efficacy variables studied were change from baseline of stool form at week 2, and satisfactory relief of IBS-related abdominal pain/discomfort and global IBS-D symptoms. Secondary efficacy variables, pharmacokinetics and safety were also evaluated.RESULTSIn total, 315 subjects were randomised. There were no statistically significant differences between treatment groups for the primary efficacy variables. However, analysis of combined data from both trials revealed significant differences favouring DNK333 25 mg over placebo for satisfactory relief of IBS-related abdominal pain/discomfort and global IBS-D symptoms. Trends favouring improvement with DNK333 25 mg vs. placebo were seen for all secondary efficacy variables. DNK333 had a safety profile similar to placebo.CONCLUSIONSDNK333 25 mg b.d. appears to be effective and well tolerated in women with IBS-D. Further studies with neurokinin antagonists are warranted.

2008-07-01·British Journal of Pharmacology2区 · 医学

In vivo pharmacological evaluation of compound 48/80‐induced airways oedema by MRI

2区 · 医学

Article

作者: C. Cannet ; S. Zurbruegg ; N. Beckmann ; F. X. Blé ; Harry Karmouty-Quintana ; J. R. Fozard ; C. P. Page

Background and purpose:Allergen‐induced airways oedema in actively sensitized rats has been studied earlier by magnetic resonance imaging (MRI). We used MRI to follow the consequences of non‐immunological mast cell activation induced by compound 48/80 in the rat lungs in vivo.Experimental approach:Male naïve rats were scanned by MRI prior to and at several time points following intratracheal administration of the mast cell secretagogue, compound 48/80. The effects of a range of drugs on the response induced by compound 48/80 were studied.Key results:Strong fluid signals were detected by MRI in the lungs at 24 h after compound 48/80, correlating with increased protein concentration and inflammatory cell infiltration in bronchoalveolar lavage, and with perivascular oedema observed histologically. Pharmacological intervention demonstrated that the increase in MRI signal volume induced by compound 48/80 24 h after challenge was blocked by disodium cromoglycate and the glucocorticoid, budesonide. Pretreatment with wortmannin, capsazepine, DNK333 (a dual neurokinin (NK) 1 and NK2 antagonist) or the anti‐allergy drug CGS8515, but not indomethacin, resulted in partial inhibition.Conclusions and implications:Compound 48/80 induced a complex inflammatory reaction which did not solely involve mast cell degranulation but also activation of sensory nerves and was qualitatively similar to allergen challenge. Changes observed by MRI correlated with decreases in protein concentration in BAL fluid. However, the magnitude of the changes detected was greater using MRI. Our results demonstrate that MRI is a sensitive and efficient tool to assess the effects of drugs on lung inflammation.British Journal of Pharmacology (2008) 154, 1063–1072; doi:10.1038/bjp.2008.174; published online 12 May 2008

2007-08-01·Pulmonary Pharmacology & Therapeutics3区 · 医学

Animal models of cough: Literature review and presentation of a novel cigarette smoke-enhanced cough model in the guinea-pig

3区 · 医学

Article

作者: C. Winny ; C. Ambrose ; K. Banner ; K. Butler ; C. Battram ; J. Giddings ; C. Poll ; C.A. Lewis ; J. Mok ; J. Nasra

A wealth of literature describes the approaches that investigators have used to develop animal models of cough. The relevance of the models to cough in man and disease is still unknown. Furthermore, the choice of animal model that is used will depend on the purpose of the investigation and what questions are being asked. Cigarette smoke is known to cause COPD and cough is a principle symptom where patients demonstrate an increased cough response to citric acid or capsaicin. This paper describes the development of exacerbated cough to these agents in the guinea-pig following cigarette smoke exposure and pharmacological profiling of these models. Male Dunkin-Hartley guinea-pigs were exposed to air or cigarette smoke (4 or 5 research cigarettes daily for the capsaicin and citric acid studies, respectively) for a 3 s puff every 30 s, for up to 10 days. At selected time points conscious, unrestrained animals were placed in a plethysmograph chamber and challenged with an aerosol of 0.3 M citric acid (10 min) or 10 microM capsaicin (7 min). Cough and Penh area under the curve (AUC) were recorded during the exposure and for a further 10 min (citric acid) or 8 min (capsaicin) after exposure. Compounds were administered on day 3 or 11 for citric acid or capsaicin, respectively. Significant enhancement of citric acid-induced cough was evident 24 h (12+/-2 to 24+/-4* coughs) after a single exposure and further enhanced after 2 days (13+/-3 to 36+/-4* coughs). Enhanced cough to capsaicin was not reliable until after 10 days of cigarette smoke exposure (2+/-1 to 14+/-3** coughs). Data are expressed as mean+/-s.e.mean (n=10), *p<0.05, **p<0.01 vs. air-exposed animals (Mann-Whitney rank-sum test). The minimum effective doses to inhibit citric acid-induced cough were 10, 10, 3 and 0.3 mg/kg for codeine (p.o. -30 min), a selective NK(1)/NK(2) antagonist, DNK333 (p.o. -2 h), terbutaline (s.c. -1 h) and atropine (s.c. -1 h), respectively. The minimum effective doses to inhibit capsaicin-induced cough were 3, 1, 0.3 and 0.3 mg/kg for codeine, DNK333, terbutaline (p.o. -2 h) and atropine, respectively. The VR1 antagonists capsazepine and iodo-resiniferatoxin (IRTX) did not inhibit cough in either model. Differences in sensitivity between citric acid and capsaicin to pharmacological agents may be partly explained by the difference in magnitude of response to these agents. Clinically used compounds such as codeine and terbutaline have shown activity in both models, however the relevance of the models to cough in man and disease for potential new therapies is unknown.

100 项与 DNK-333 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
特应性皮炎	临床2期	德国	Novartis Pharmaceuticals Corp.	2009-11-01
腹泻型肠易激综合征	临床2期	加拿大	Novartis AG	2006-09-01
腹泻型肠易激综合征	临床2期	美国	Novartis AG	2006-09-01
咳嗽	临床2期	荷兰	Novartis AG	2003-09-01
咳嗽	临床2期	英国	Novartis AG	2003-09-01
慢性阻塞性肺疾病	临床2期	英国	Novartis AG	2003-09-01
慢性阻塞性肺疾病	临床2期	荷兰	Novartis AG	2003-09-01