卡索匹坦(Casopitant Mesylate) - 药物靶点：NK1R_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Casopitant、Casopitant mesylate (USAN)、Rezonic

+ [4]

靶点

NK1R

作用机制

NK1R 拮抗剂(神经激肽-1-受体拮抗剂)

治疗领域

其他疾病肿瘤神经系统疾病+ [2]

在研适应症-

非在研适应症

焦虑症化疗引起的恶心和呕吐重度抑郁症+ [13]

原研机构

GSK Plc

在研机构-

非在研机构

GSK Plc

最高研发阶段终止申请上市

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C31H39F7N4O5S

InChIKeyYRFKYVWDPCOSTE-REWBLLDVSA-N

CAS号414910-30-8

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关联

48

项与卡索匹坦相关的临床试验

NCT00891761 / Withdrawn临床3期

A Study of Single Dose Intravenous Casopitant in Combination With Ondansetron and Dexamethasone for the Prevention of Cisplatin-Induced Nausea and Vomiting

This is a phase III study designed to demonstrate the superiority of single-dose 90 mg intravenous (IV) casopitant over placebo, each in combination with ondansetron and dexamethasone, for the prevention of emesis over the first 0-120 hours (overall phase) following initiation of the cisplatin infusion in the first cycle of highly emetogenic chemotherapy (HEC). Eligibility is limited to subjects who are scheduled to receive their first cycle of chemotherapy which includes at least 60 mg/m2 of cisplatin administered on Day 1 only of a 21 day or 28 day cycle. All subjects will receive IV ondansetron and oral dexamethasone on Day 1 prior to initiation of the cisplatin infusion, followed by oral dexamethasone on Days 2-4. Additionally, subjects will be randomized to receive single-dose 90 mg IV casopitant or matching placebo prior to initiation of a cisplatin-based HEC regimen.

开始日期2009-09-01

申办/合作机构

GSK Plc

NCT00601172 / Completed临床3期

A Study of Single Dose Intravenous Casopitant in Combination With Ondansetron and Dexamethasone for the Prevention of Oxaliplatin Induced Nausea and Vomiting.

This a Phase III trial designed to determine if IV casopitant plus dexamethasone and ondansetron is more effective in the prevention of vomiting and nausea then dexamethasone and ondansetrone alone following the administration of moderately emetogenic oxaliplatin-based chemotherapy.

开始日期2008-03-10

申办/合作机构

GSK Plc

EUCTR2007-005169-36-IT / Not yet recruitingN/A

A Study of Single Dose Intravenous Casopitant in Combination with Ondansetron and Dexamethasone for the Prevention of Oxaliplatin-Induced Nausea and Vomiting - Casopitant in prevention of nausea and vomiting

开始日期2008-02-05

申办/合作机构

GlaxoSmithKline Research & Development Ltd.

100 项与卡索匹坦相关的临床结果

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100 项与卡索匹坦相关的转化医学

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100 项与卡索匹坦相关的专利（医药）

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51

项与卡索匹坦相关的文献（医药）

2024-02-01·Biotechnology and Applied Biochemistry

Homology modeling, virtual screening, molecular docking, and ADME approaches to identify a potent agent targeting NK2R protein

Article

作者: Soltani, Arash ; Hashemy, Seyed Isaac

AbstractNeurokinin/tachykinin receptors are classified as the G‐protein coupled receptor superfamily. The neurokinin 2 receptor (NK2R) is widely expressed in different tissues. NK2R is associated with a range of biological events, such as inflammation, smooth muscle contraction, intestinal motor functions, and asthma. Despite these diverse activities, no approved drugs targeting NK2R have been developed yet. Our study focuses on finding potential inhibitors for NK2R using virtual screening, molecular docking, and ADME (absorption, distribution, metabolism, and excretion) approaches. We used a homology modeling approach and AlphaFold DB to obtain the three‐dimensional structure of mouse and human NK2R proteins, respectively. The homology model of NK2R was predicted using MODELLER v10.3 and further refined and validated using the 3Drefine tool and RAMPAGE server, respectively. Molecular docking was performed using a library of 910 structurally similar molecules to four NK1R antagonists: aprepitant, casopitant, fosaprepitant, and rolapitant. Molecular docking revealed six small molecules that displayed high Chemscore fitness scores, and binding energies with desirable ligand–NK2R interactions. The evaluation of the in silico ADME profile, solubility, and permeability of the ligand molecules has revealed that the small molecules are potentially nontoxic and have the chance of exhibiting biological activity after oral administration. Further experimental studies (in vitro and in vivo assays) are required to evaluate the effectiveness of these inhibitors as therapeutic targets.

2022-07-01·Pharmacopsychiatry

Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry

Review

作者: Tani, Hideaki ; Sakurai, Hitoshi ; Yonezawa, Kengo ; Uchida, Hiroyuki ; Mimura, Masaru ; Bauer, Michael

Abstract Introduction There is an imminent need for faster-acting and more effective antidepressants beyond the monoaminergic hypothesis. Methods We systematically searched the US Clinical Trials registry for antidepressant compounds with completed phase II and III trials. Compounds that demonstrated significant superiority over placebo in the primary outcome measure in the latest phase of phase II and III trials were identified. The collateral information was gathered via a PubMed search and press releases. Results Nine compounds were identified. AXS-05 (a combination of dextromethorphan and bupropion) and ansofaxine hydrochloride showed a positive result over placebo in a phase III study for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, facial injection of botulinum toxin A, prasterone, and casopitant demonstrated at least one positive result in phase II trials. Ayahuasca showed a greater response rate than placebo at week one, indicating the rapid antidepressant effect. Discussion These new compounds with novel mechanisms of action are expected to provide a greater variety of treatment options for depression if preliminary positive results are confirmed.

2018-05-01·The Oncologist2区 · 医学

Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy: A Network Meta-Analysis

2区 · 医学

Review

作者: Gao, Fangfang ; Zhao, Hongyun ; Yang, Yunpeng ; Huang, Yan ; Zhang, Yaxiong ; Zhang, Li ; Hong, Shaodong ; Chen, Likun ; Chen, Xi ; Zhang, Zhonghan ; Ma, Shuxiang ; Zhou, Ningning ; Chen, Gang ; Luo, Fan ; Ma, Yuxiang ; Hou, Xue ; Xue, Cong ; Zhou, Ting ; Fang, Wenfeng ; Zhan, Jianhua ; Zhao, Yuanyuan

AbstractBackgroundThe current antiemetic prophylaxis for patients treated with highly emetogenic chemotherapy (HEC) included the olanzapine-based triplet and neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one shows better antiemetic effect remained unclear.Materials and MethodsWe systematically reviewed 43 trials, involving 16,609 patients with HEC, which compared the following antiemetics at therapeutic dose range for the treatment of chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant, fosaprepitant, netupitant, and rolapitant. The main outcomes were the proportion of patients who achieved no nausea, complete response (CR), and drug-related adverse events. A Bayesian network meta-analysis was performed.ResultsOlanzapine-based triple regimens showed significantly better no-nausea rate in overall phase and delayed phase than aprepitant-based triplet (odds ratios 3.18, 3.00, respectively), casopitant-based triplet (3.78, 4.12, respectively), fosaprepitant-based triplet (3.08, 4.10, respectively), rolapitant-based triplet (3.45, 3.20, respectively), and conventional duplex regimens (4.66, 4.38, respectively). CRs of olanzapine-based triplet were roughly equal to different NK-1RAs-based triplet but better than the conventional duplet. Moreover, no significant drug-related adverse events were observed in olanzapine-based triple regimens when compared with NK-1RAs-based triple regimens and duplex regimens. Additionally, the costs of olanzapine-based regimens were obviously much lower than the NK-1RA-based regimens.ConclusionOlanzapine-based triplet stood out in terms of nausea control and drug price but represented no significant difference of CRs in comparison with NK-1RAs-based triplet. Olanzapine-based triple regimens should be an optional antiemetic choice for patients with HEC, especially those suffering from delayed phase nausea.Implications for PracticeAccording to the results of this study, olanzapine-based triple antiemetic regimens were superior in both overall and delayed-phase nausea control when compared with various neurokinin-1 receptor antagonists-based triple regimens in patients with highly emetogenic chemotherapy (HEC). Olanzapine-based triplet was outstanding in terms of nausea control and drug price. For cancer patients with HEC, especially those suffering from delayed-phase nausea, olanzapine-based triple regimens should be an optional antiemetic choice.

100 项与卡索匹坦相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06574	卡索匹坦	-	DB06634

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
呕吐	申请上市	爱尔兰	GSK Plc	2006-03-01
呕吐	申请上市	比利时	GSK Plc	2006-03-01
呕吐	申请上市	比利时	GSK Plc	2006-03-01
呕吐	申请上市	爱尔兰	GSK Plc	2006-03-01
化疗引起的恶心和呕吐	申请上市	美国	GSK Plc	-
化疗引起的恶心和呕吐	申请上市	美国	GSK Plc	-
化疗引起的恶心和呕吐	申请上市	欧盟	GSK Plc	-
化疗引起的恶心和呕吐	申请上市	欧盟	GSK Plc	-
术后恶心呕吐	申请上市	欧盟	GSK Plc	-
术后恶心呕吐	申请上市	欧盟	GSK Plc	-

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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


NCT00601172 (CTgov)	临床3期	恶心 \| 化疗引起的恶心和呕吐 \| 呕吐	710	placebo+casopitant+Ondansetron+dexamethasone (Placebo)	範鬱繭顧繭製膚簾製鏇(範醖淵觸鏇衊壓獵糧蓋) = 窪鬱夢淵遞壓窪壓鏇夢鏇範夢蓋鹹鑰窪壓壓築 (觸鬱膚鑰鹹顧襯範簾鏇, 齋簾鏇顧淵窪繭衊製築 ~ 淵鹹廠壓憲餘壓願夢餘) 更多	-	2018-01-17
				Casopitant (Casopitant 90 mg)	範鬱繭顧繭製膚簾製鏇(範醖淵觸鏇衊壓獵糧蓋) = 壓築醖憲鏇艱壓壓構艱鏇範夢蓋鹹鑰窪壓壓築 (觸鬱膚鑰鹹顧襯範簾鏇, 鬱鏇襯範襯觸鏇鬱遞鏇 ~ 鏇構衊蓋願齋簾壓顧觸) 更多
ASCO2011	临床3期	药物引起的恶心和呕吐	710	Casopitant 90 mg	(製顧鹹積簾蓋廠壓鏇艱) = 簾淵遞繭顧醖夢鹹簾窪鏇製艱衊廠繭構構膚膚 (簾構蓋鹹衊壓鏇廠夢餘 )	-	2011-05-20
				Placebo	(製顧鹹積簾蓋廠壓鏇艱) = 淵構窪製衊繭鬱壓願製鏇製艱衊廠繭構構膚膚 (簾構蓋鹹衊壓鏇廠夢餘 )
Pubmed \| Anesth Analg	临床2期	术后恶心呕吐	702	Ondansetron 4 mg	(鏇膚醖積築齋築積衊窪) = headache, dizziness, and constipation were the most frequently reported adverse events 蓋糧齋築鹹鏇醖醖願構 (鏇襯醖鬱繭鏇積淵繭夢 ) 更多	积极	2010-07-01
				Casopitant 0 mg
NCT00104403 (Pubmed \| Cancer)	临床2期	肿瘤	723	Casopitant 50 mg	(醖衊醖憲憲夢簾鏇艱淵) = 鹽遞膚襯艱襯艱製遞壓膚襯簾糧衊網願壓製窪 (艱衊獵齋淵膚遞糧鬱選 ) 更多	积极	2009-12-15
				Casopitant 100 mg	(醖衊醖憲憲夢簾鏇艱淵) = 壓簾鹽積鏇淵壓願遞構膚襯簾糧衊網願壓製窪 (艱衊獵齋淵膚遞糧鬱選 ) 更多
NCT00366834 (Pubmed \| J Urol)	临床3期	化疗引起的恶心和呕吐	1,840	Control	(憲獵艱憲鏇鬱願醖餘網) = 遞鑰觸遞鹽獵餘窪夢願淵構願鹽憲膚窪鹹齋築 (選醖淵築觸鑰鑰鹹艱餘 )	积极	2009-11-10
				Single-dose oral casopitant	(憲獵艱憲鏇鬱願醖餘網) = 製窪艱夢餘範夢憲遞選淵構願鹽憲膚窪鹹齋築 (選醖淵築觸鑰鑰鹹艱餘 )
NCT00431236 (Pubmed \| Lancet Oncol)	临床3期	化疗引起的恶心和呕吐	810	Casopitant mesylate (single oral dose)	(餘憲鏇簾壓艱糧鹽鹹鑰) = 糧遞憲遞糧顧鑰鹽蓋選壓鬱築壓築齋選艱鹽選 (鑰繭蓋齋齋艱憲繭壓醖 )	积极	2009-06-01
				Casopitant mesylate (3-day intravenous plus oral)	(餘憲鏇簾壓艱糧鹽鹹鑰) = 窪製積鏇餘夢遞顧襯觸壓鬱築壓築齋選艱鹽選 (鑰繭蓋齋齋艱憲繭壓醖 )
ASCO2006	临床2期	化疗引起的恶心和呕吐	493	Placebo control	(蓋構壓蓋獵築構壓選積) = 鹽夢網選觸鹹觸構艱衊膚獵願簾獵艱蓋繭願鑰 (夢顧淵築廠艱襯襯鏇廠 ) 更多	-	2006-06-20
				Casopitant 50mg	(蓋構壓蓋獵築構壓選積) = 選鑰簾築鹹構觸窪憲憲膚獵願簾獵艱蓋繭願鑰 (夢顧淵築廠艱襯襯鏇廠 ) 更多
ASCO2006	临床2期	化疗引起的恶心和呕吐	719	Casopitant mesylate 50mg	(蓋願獵鏇願觸繭餘襯糧) = 壓鏇獵襯憲鹹夢憲壓淵餘鏇鏇餘願遞築簾壓衊 (壓襯夢網衊鏇鹽餘鏇繭 )	-	2006-06-20
				Casopitant mesylate 100mg	(蓋願獵鏇願觸繭餘襯糧) = 膚鹹築衊選壓願齋餘顧餘鏇鏇餘願遞築簾壓衊 (壓襯夢網衊鏇鹽餘鏇繭 )