阿卤芬酯(Arhalofenate) - 药物靶点：PPARγ x URAT1_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Arhalofenate (USAN/INN)、Metaglidasen

+ [3]

靶点

PPARγ x URAT1

作用机制

PPARγ拮抗剂(过氧化物酶体增长因子活化受体γ拮抗剂)、URAT1抑制剂(尿酸盐重吸收转运子抑制剂)

治疗领域

遗传病与畸形内分泌与代谢疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症-

非在研适应症

2型糖尿病痛风高尿酸血症

原研机构

CymaBay Therapeutics, Inc.

在研机构-

非在研机构

CymaBay Therapeutics, Inc.

西安杨森制药有限公司

Kowa Co., Ltd.

+ [1]

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)终止

特殊审评-

结构

分子式C19H17ClF3NO4

InChIKeyBJBCSGQLZQGGIQ-QGZVFWFLSA-N

CAS号24136-23-0

关联

7

项与阿卤芬酯相关的临床试验

NCT02252835 / Completed临床2期

A Phase 2, Open-label, Drug-Drug Interaction Study to Evaluate the Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination With Febuxostat for the Treatment of Hyperuricemia in Patients With Gout

The purpose of this study is to evaluate pharmacokinetics, pharmacodynamics, safety and potential for drug-drug interaction of arhalofenate when combined with febuxostat in adult population with gout.

开始日期2014-08-01

申办/合作机构

CymaBay Therapeutics, Inc.

NCT02063997 / Completed临床2期

A Randomized, Double-Blind, Active and Placebo-Controlled Study to Evaluate the Efficacy and Safety of Arhalofenate for Preventing Flares and Reducing Serum Uric Acid in Gout Patients

The purpose of this study is to determine whether arhalofenate is effective in preventing flares and reducing serum uric acid in gout patients.

开始日期2014-03-01

申办/合作机构

CymaBay Therapeutics, Inc.

NCT01416402 / Completed临床2期

A Phase 2, Open-label Study to Evaluate the Safety and Efficacy of Arhalofenate (MBX-102) in Combination With Febuxostat for the Treatment of Hyperuricemia in Patients With Gout

The purpose of this study is to determine whether arhalofenate is safe and effective when dosed in combination with febuxostat in lowering serum uric acid in patients with gout.

开始日期2011-08-31

申办/合作机构

CymaBay Therapeutics, Inc.

100 项与阿卤芬酯相关的临床结果

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100 项与阿卤芬酯相关的转化医学

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100 项与阿卤芬酯相关的专利（医药）

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30

项与阿卤芬酯相关的文献（医药）

2024-03-01·Current Rheumatology Reports

Pipeline Therapies for Gout

Review

作者: Braverman, Genna ; Yue, Linda ; Fields, Theodore ; Yip, Kevin

PURPOSE OF REVIEWDespite effective available treatments, gout management is often unsuccessful in getting patients to target serum urate goal and in managing flares in the setting of comorbidities. Studies addressing future treatment options for short- and long-term management are reviewed.RECENT FINDINGSURAT-1 blocking agents have been helpful but have had limitations related to effects on renal function, lack of efficacy with renal impairment, and potential to increase renal stones. Dotinurad may function in the setting of decreased renal function. Arhalofenate has anti-URAT-1 activity and may also blunt gout flares. A new xanthine oxidase inhibitor (XOI), tigulixostat, is under study. New uricase treatments manufactured in combination with agents that can reduce immunogenicity may make uricase treatment simpler. A unique strategy of inhibiting gut uricase may offer the benefits of avoiding systemic absorption. For gout flares, IL-1β inhibitor studies in progress include different dosing schedules. Dapansutrile, an oral agent under investigation, inhibits activation of the NLRP3 inflammasome and may be an effective anti-inflammatory. New treatments for gout that are under study may work in the setting of comorbidities, simplify management, utilize new mechanisms, or have reduced side effects.

2023-12-02·Expert Opinion on Drug Metabolism & Toxicology

Overview of the pharmacokinetics and pharmacodynamics of URAT1 inhibitors for the treatment of hyperuricemia and gout

Review

作者: Song, Danni ; Mao, Jiale ; Hou, Zihan ; Ma, Aijinxiu ; Zhao, Xu

INTRODUCTIONHyperuricemia is a common metabolic disease, which is a risk factor for gouty arthritis and ureteral stones and may also lead to cardiovascular and chronic kidney disease (CDK). Therefore, hyperuricemia should be treated early. Xanthine oxidase inhibitors (XOIs) and uricosuric agents (UAs), which target uric acid, are two types of medications that are used to treat gout and hyperuricemia. XOIs stop the body from producing excessive uric acid, while UAs eliminate it rapidly via the kidneys. Urate transporter 1 (URAT1) belongs to the organic anion transporter family (OAT) and is specifically localized to the apical membrane of the epithelial cells of proximal tubules. Unlike other organic anion transporter family members, URAT1 identifies and transports organic anions that are primarily responsible for urate transport.AREAS COVEREDThis article reviews the pharmacokinetics and pharmacodynamics of the existing URAT1 inhibitors to serve as a reference for subsequent drug studies.EXPERT OPINIONThe URAT1 inhibitors that are currently used as clinical drugs mainly include dotinurad, benzbromarone, and probenecid. Results indicate that RDEA3170 may be the most promising inhibitor, in addition to SHR4640, URC-102, and MBX-102, which are in the early stages of development.

2022-03-24·The Journal of Clinical Endocrinology & Metabolism2区 · 医学

CAR-T Cells Targeting TSHR Demonstrate Safety and Potent Preclinical Activity Against Differentiated Thyroid Cancer

2区 · 医学

Article

作者: Du, Yaying ; Cai, Miaomiao ; Yang, Zhifang ; Wang, Ge ; Li, Hanning ; Zhang, Tongcun ; Li, Xingrui ; Wu, Yonglin ; Zhou, Xiang ; Liao, Xinghua ; Xu, Tao ; Li, Shuyu ; Hua, Dongyu ; Dong, Menglu ; Yang, Xue ; Cui, Xiaoqing

AbstractBackgroundChimeric antigen receptor T cells (CAR-Ts) have demonstrated remarkable efficacy in hematological cancers but have not yet translated in treating solid tumors. The significant hurdles limiting CAR-T therapy were from a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present TSH receptor (TSHR) as a putative target for CAR-T therapy of differentiated thyroid cancer (DTC).MethodsWe undertook a large-scale screen on thyroid cancer tissues and multiple internal organs through bioinformatical analysis and immunohistochemistry to date TSHR expression. Using 3 previously described monoclonal antibodies, we generated 3 third-generation CAR-Ts. We tested anti-TSHR CAR-T in vitro activity by T-cell function and killing assay. Then we tested preclinical therapeutical efficacy in a xenograft mouse model of DTC and analyzed mice’s physical conditions and histological abnormalities to evaluate anti-TSHR CAR-T’s safety.ResultsTSHR is highly and homogeneously expressed on 90.8% (138/152) of papillary thyroid cancer, 89.2% (33/37) of follicular thyroid cancer, 78.2% (18/23) of cervical lymph node metastases, and 86.7% of radioactive iodine resistance diseases. We developed 3 novel anti-TSHR CAR-Ts from monoclonal antibodies M22, K1-18, and K1-70; all 3 CAR-Ts mediate significant antitumor activity in vitro. Among these, we demonstrate that K1-70 CAR-T can have therapeutical efficacy in vivo, and no apparent toxicity has been observed.ConclusionTSHR is a latent target antigen of CAR-T therapy for DTC. Anti-TSHR CAR-T could represent a therapeutic option for patients with locoregional relapsed or distant metastases of thyroid cancer and should be tested in carefully designed clinical trials.

100 项与阿卤芬酯相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09579	-	-	DB11811

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
高尿酸血症	临床3期	美国	CymaBay Therapeutics, Inc.	2011-05-31
2型糖尿病	临床3期	美国	CymaBay Therapeutics, Inc.	2006-05-01
痛风	临床3期	-	Kowa Co., Ltd.	-
2型糖尿病	临床2期	印度	CymaBay Therapeutics, Inc.	2006-05-01
痛风	临床2期	-	Kowa Co., Ltd.	-
2型糖尿病	临床前	阿根廷	CymaBay Therapeutics, Inc.	2006-05-01
2型糖尿病	药物发现	以色列	CymaBay Therapeutics, Inc.	2006-05-01

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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


NCT02252835 (EULAR2015)	临床2期	痛风	-	Arhalofenate 600 mg	觸網鏇壓範觸積壓壓選(糧遞醖鬱壓齋獵願艱顧) = one case of elevated transaminases that emerged after the initiation of febuxostat 窪夢遞衊遞顧糧糧鬱鹹 (鑰廠遞選壓簾艱淵顧蓋 ) 更多	-	2015-06-10
				Febuxostat 80 mg
NCT02252835 (Pubmed \| J Rheumatol)	临床2期	痛风	32	Arhalofenate 600 mg + Febuxostat 80 mg	遞築壓襯鑰繭顧廠夢願(鹹窪願鏇鬱窪鑰鏇網築) = 鏇積遞壓窪鹽鑰繭顧獵鏇鏇遞構構壓蓋餘襯願 (築鑰繭壓鹽蓋鹹壓憲遞 ) 更多	-	2017-03-01
				Arhalofenate 800 mg + Febuxostat 40 mg	遞築壓襯鑰繭顧廠夢願(鹹窪願鏇鬱窪鑰鏇網築) = 鑰積蓋廠鏇鹹鑰鏇鹽蓋鏇鏇遞構構壓蓋餘襯願 (築鑰繭壓鹽蓋鹹壓憲遞 ) 更多
EULAR2012	N/A	-	-	Arhalofenate acid	網簾繭壓餘蓋齋簾夢淵(糧鹽構鹽餘鹹繭淵製鏇) = 簾鏇窪餘憲製簾範網選構簾醖淵淵糧網艱艱壓 (繭蓋遞繭壓獵齋鹹衊鏇 ) 更多	-	2012-06-06
				Probenecid	餘衊選構製網製憲獵蓋(鹽鏇範願鬱願膚艱壓繭) = 繭憲膚獵繭鏇網積淵蓋窪築餘築構膚窪製蓋選 (淵製選願窪淵壓襯願築 ) 更多
NCT01399008 (CTgov)	临床2期	痛风	100	Allopurinol+Colchicine+Arhalofenate (Arhalofenate 400 mg)	選觸遞網範醖齋積製淵(選鏇繭顧顧蓋憲遞選遞) = 窪齋壓膚網願鬱繭構遞淵艱膚餘範鬱窪鏇鹹壓 (鹽構繭壓廠蓋膚襯築齋, 淵築繭夢製遞餘膚積齋 ~ 襯醖鏇構構積鑰鏇積糧)	-	2014-07-28
				Allopurinol+Colchicine+Arhalofenate (Arhalofenate 600 mg)	選觸遞網範醖齋積製淵(選鏇繭顧顧蓋憲遞選遞) = 鹹糧鑰構襯夢積餘淵壓淵艱膚餘範鬱窪鏇鹹壓 (鹽構繭壓廠蓋膚襯築齋, 艱願鏇選衊壓築憲願積 ~ 憲鏇築衊艱積醖遞鏇糧)