扎托洛芬(Zaltoprofen) - 药物靶点：COX_在研适应症：镇痛，炎症，疼痛_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Pyranoprofen、Zaltoprofen (JP17/INN)

+ [6]

靶点

COX

作用机制

COX抑制剂(环氧化酶抑制剂)

治疗领域

神经系统疾病其他疾病

在研适应症

镇痛炎症疼痛

非在研适应症-

原研机构

Zeria Pharmaceutical Co., Ltd.

在研机构

Nippon Chemiphar Co., Ltd.

Zeria Pharmaceutical Co., Ltd.

非在研机构-

最高研发阶段批准上市

首次获批日期

日本 (1993-07-02),

镇痛炎症疼痛

最高研发阶段(中国)-

特殊审评-

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结构

分子式C17H14O3S

InChIKeyMUXFZBHBYYYLTH-UHFFFAOYSA-N

CAS号74711-43-6

关联

5

项与扎托洛芬相关的临床试验

JPRN-jRCT2091220284 / Completed临床2期IIT

Placebo-controlled randomized, double-blind study of zaltoprofen for patients with diffuse type tenosynovial giantcell tumor (Pigmented Villonodular Synovitis) and unresectable localized tenosynovial giant cell tumor (tendon sheath giant cell tumor) (Phase II study) - TGCT Clinical trial

开始日期2017-04-28

申办/合作机构

Kanazawa University Hospital

JPRN-JMA-IIA00284 / Completed临床2期IIT

Placebo-controlled randomized, double-blind study of zaltoprofen for patients with diffuse type tenosynovial giantcell tumor (Pigmented Villonodular Synovitis) and unresectable localized tenosynovial giant cell tumor (tendon sheath giant cell tumor) (Phase II study)

开始日期2017-04-28

申办/合作机构

Kanazawa University Hospital

JPRN-UMIN000025901 / Completed临床2期IIT

Placebo-controlled randomized, double-blind study of zaltoprofen for patients with diffuse type tenosynovial giant cell tumor (Pigmented Villonodular Synovitis) and unresectable localized tenosynovial giant cell tumor (tendon sheath giant cell tumor) (Phase II study) - Placebo-controlled randomized, double-blind Phase II study of zaltoprofen for patients with diffuse type tenosynovial giant cell tumor and unresectable localized tenosynovial giant cell tumor

开始日期2017-04-04

申办/合作机构

Kanazawa University

100 项与扎托洛芬相关的临床结果

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100 项与扎托洛芬相关的转化医学

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100 项与扎托洛芬相关的专利（医药）

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93

项与扎托洛芬相关的文献（医药）

2023-09-01·Chemico-biological interactions

Effects of acidic non-steroidal anti-inflammatory drugs on human cytochrome P450 4A11 activity: Roles of carboxylic acid and a sulfur atom in potent inhibition by sulindac sulfide.

Article

作者: Yamaori, Satoshi ; Masuda, Kazufumi ; Yamashita, Naho ; Itoh, Hisataka ; Kamijo, Shinobu ; Kato, Hisato

Cytochrome P450 4A11 (CYP4A11) has many endogenous and exogenous compounds containing a carboxyl group in their structure as substrates. If drugs with this characteristic potently attenuate the catalytic function of CYP4A11, drug-drug interactions may occur. Acidic non-steroidal anti-inflammatory drugs (NSAIDs) possess a carboxylic acid in their structure. However, it remains unclear whether these drugs inhibit CYP4A11 activity. The present study examined the inhibitory effects of acidic NSAIDs on CYP4A11 activity using human liver microsomes (HLMs) and recombinant CYP4A11. Sulindac sulfide, ibuprofen, and flurbiprofen effectively decreased the luciferin-4A O-demethylase activity of HLMs and recombinant CYP4A11 (inhibition rates of 30-96% at an inhibitor concentration of 100 μM), while salicylic acid, aspirin, diclofenac, mefenamic acid, indomethacin, etodolac, ketoprofen, loxoprofen, S-naproxen, pranoprofen, zaltoprofen, and oxaprozin exhibited weaker inhibitory activity (inhibition rates up to 23%). Among the drugs tested, sulindac sulfide was the most potent inhibitor of CYP4A11 activity. A kinetic analysis of the inhibition of CYP4A11 by sulindac sulfide revealed mixed-type inhibition for HLMs (K_i = 3.38 μM) and recombinant CYP4A11 (K_i = 4.19 μM). Sulindac sulfide is a pharmacologically active metabolite of sulindac (sulfoxide form), which is also oxidized to sulindac sulfone. To elucidate the role of a sulfur atom of sulindac sulfide in the inhibition of CYP4A11, the inhibitory effects of sulindac sulfide and its oxidized forms on CYP4A11 activity were examined. The potency of inhibition against HLMs was greater in the order of sulindac sulfide, sulindac, and sulindac sulfone; IC₅₀ values were 6.16, 52.7, and 71.6 μM, respectively. The present results indicate that sulindac sulfide is a potent inhibitor of CYP4A11. These results and the molecular modeling of CYP4A11 with sulindac sulfide and its oxidized forms suggest that a sulfur atom of sulindac sulfide as well as its carboxylic acid play important roles in the inhibition of CYP4A11.

2023-04-18·Cell Cycle

A nonsteroidal anti-inflammatory drug, zaltoprofen, inhibits the growth of extraskeletal chondrosarcoma cells by inducing PPARγ, p21, p27, and p53

Article

作者: Munesue, Seiichi ; Hayashi, Katsuhiro ; Yamamoto, Yasuhiko ; Harashima, Ai ; Higuchi, Takashi ; Takeuchi, Akihiko ; Yamamoto, Norio ; Tsuchiya, Hiroyuki

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and master transcription factor of adipogenesis-related genes, and has been reported as an antitumor target for chondrosarcomas. Herein, we show that the nonsteroidal anti-inflammatory drug, zaltoprofen, induces the expression of PPARγ at the mRNA and protein levels, following the induction of PPARγ-activating factors, such as Krox20, C/EBPβ, and C/EBPα, in human extraskeletal chondrosarcoma H-EMC-SS cells. Upregulation of the cell cycle checkpoint proteins, p21, p27, and p53, was observed upon treatment of H-EMC-SS cells with zaltoprofen, which probably resulted in the inhibition of proliferation of these cells observed in vitro. Zaltoprofen treatment inhibited tumor growth, induced tumor cell apoptosis, and was well tolerated in a mouse model of extraskeletal myxoid chondrosarcoma. Our results provide mechanistic insights into the therapeutic effect of zaltoprofen that should promote further studies on the rational use of this drug for the effective treatment of sarcomas.

2023-04-01·Contemporary Clinical Trials Communications

Application of sequential multimodal analgesia before and after impacted mandibular third molar extraction: Protocol for a randomized controlled trial

Article

作者: Kim, Yoon-Seon ; Kim, Somi ; Kim, Soo-Ho ; Kang, Ji-Yeon ; Song, Mi-Kyoung

BackgroundSeveral analgesics have been applied under various protocols to control the moderate-to-severe postoperative pain caused by the surgical extraction of an impacted mandibular third molar. However, a consensus on optimal pain management while minimizing side effects is yet to be reached.MethodsThis multi-center, prospective, double-blind, randomized controlled trial aims to evaluate the efficacy and safety of sequential multimodal analgesia combined with postoperative zaltoprofen along with multiple preemptive analgesics. A total of 80 participants with bilateral impacted mandibular third molar from two hospitals were randomized into two groups. Two surgical extractions were performed at one-month intervals, and in a crossover design, celecoxib or tramadol/acetaminophen was administered before one extraction and placebo before the other extraction. Following extraction, all subjects took zaltoprofen for 5 days. The outcome measures included pain at specific times, time and intensity of the first pain onset after extraction, need of rescue drugs, and occurrence and frequency of side effects.ConclusionsThis ongoing clinical trial was designed to provide evidence regarding a new protocol for effective postoperative pain management of a commonly performed surgical extraction. The results of this study will provide guidance to clinicians regarding the timing and combination of oral analgesics in various oral surgeries performed under local anesthesia.Trial registrationKCT0005450, registered on October 7, 2020.

100 项与扎托洛芬相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01547	扎托洛芬	M01AE	DB06737

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
镇痛	日本	Nippon Chemiphar Co., Ltd.	1993-07-02
炎症	日本	Zeria Pharmaceutical Co., Ltd.	1993-07-02
炎症	日本	Nippon Chemiphar Co., Ltd.	1993-07-02
疼痛	日本	Zeria Pharmaceutical Co., Ltd.	1993-07-02

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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


JPRN-UMIN000025901 (ASCO2022)	临床2期	腱鞘巨细胞瘤	-	Zaltoprofen 480 mg/day	(夢糧艱襯衊構憲繭鬱遞) = 鬱鑰齋網積選網製顧糧餘艱觸製願糧鏇醖襯膚 (襯選窪範觸醖網網齋蓋 )	不佳	2022-06-02
				Placebo	(夢糧艱襯衊構憲繭鬱遞) = 艱鬱簾醖窪膚醖鏇鹹遞餘艱觸製願糧鏇醖襯膚 (襯選窪範觸醖網網齋蓋 )