(Squaric acid dibutyl ester(Squarex)) - 在研适应症：变应性接触性皮炎_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Quadratic-acid-dibutylester、SADBE、Squaric acid dibutyl ester

+ [4]

靶点-

作用机制

免疫调节剂

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Massachusetts Institute of Technology

非在研机构

Squarex

最高研发阶段临床2/3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C12H18O4

InChIKeyXBRWELTXMQSEIN-UHFFFAOYSA-N

CAS号2892-62-8

关联

7

项与 Squaric acid dibutyl ester(Squarex) 相关的临床试验

NCT05535738 / Recruiting临床2/3期IIT

Biologics and Blistering - Using a Contact Dermatitis Model With Biologic Medications to Study Skin Inflammation Through Suction Blistering

The purpose of this study is to answer: how do inflammation and anti-inflammatory skin therapies work in the skin? Inflammation is a protective response from the body's immune system to injury, disease, or irritation. It is a process by which your body's white blood cells and the things they make protect you from infection from outside invaders such as bacteria and viruses.

开始日期2022-11-15

申办/合作机构

Massachusetts Institute of Technology

NCT05414266 / Recruiting早期临床1期IIT

A Randomized, Placebo Controlled Single Site Study Evaluating Efficacy of Topical Squaric Acid Dibutyl Ester in Children and Adolescents With Alopecia Areata

The purpose of this study is to evaluate the efficacy and tolerability of squaric acid dibutylester (SADBE) in children and adolescents with alopecia areata (AA) and to evaluate effect of squaric acid dibutyl ester on patient-centered outcomes and payer relevant measures to assess treatment benefit from the patient perspective and to demonstrate value

开始日期2022-08-15

申办/合作机构

University of Texas Health Science Center at Houston

NCT04999631 / Not yet recruiting早期临床1期

Neoadjuvant Squaric Acid Dibutylester Treatment of Melanocytes in Congenital Melanocytic Nevi

A study to evaluate the safety and efficacy topical squaric acid dibutylester (SADBE) for the neoadjuvant treatment of congenital melanocytic nevi (CMN).

开始日期2022-01-01

申办/合作机构

The General Hospital Corp.

100 项与 Squaric acid dibutyl ester(Squarex) 相关的临床结果

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100 项与 Squaric acid dibutyl ester(Squarex) 相关的转化医学

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100 项与 Squaric acid dibutyl ester(Squarex) 相关的专利（医药）

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172

项与 Squaric acid dibutyl ester(Squarex) 相关的文献（医药）

2024-03-01·Journal of Ethnopharmacology

Borneol exerts its antipruritic effects by inhibiting TRPA1 and activating TRPM8

Article

作者: Yin, Liang ; Mei, Zhinan ; Luo, Miao ; Zhan, Ping ; Zhao, Zhongqiu ; He, Jinfeng ; Xiong, Hui

ETHNOPHARMACOLOGICAL RELEVANCEBorneol is a long-established traditional Chinese medicine that has been found to be effective in treating pain and itchy skin. However, whether borneol has a therapeutic effect on chronic itch and its related mechanisms remain unclear.AIM OF THE STUDYTo investigate the antipruritic effect of borneol and its molecular mechanism.MATERIALS AND METHODSDrugBAN framework and molecular docking were applied to predict the targets of borneol, and the calcium imaging or patch-clamp recording analysis were used to detect the effects of borneol on TRPA1, TRPM8 or TRPV3 channels in HEK293T cells. In addition, various mouse models of acute itch and chronic itch were established to evaluate the antipruritic effects of borneol on C57BL/6J mice. Then, the borneol-induced pruritic relief was further investigated in Trpa1^-/-, Trpm8^-/-, or Trpa1^-/-/Trpm8^-/- mice. The effects of borneol on the activation of TRPM8 and the inhibition of TRPA1 were also measured in dorsal root ganglia neurons of wild-type (WT), Trpm8^-/- and Trpv1^-/- mice. Lastly, a randomized, double-blind study of adult patients was conducted to evaluate the clinical antipruritic effect of borneol.RESULTSTRPA1, TRPV3 and TRPM8 are the potential targets of borneol according to the results of DrugBAN algorithm and molecular docking. Calcium imaging and patch-clamp recording analysis demonstrated that borneol activates TRPM8 channel-induced cell excitability and inhibits TRPA1 channel-mediated cell excitability in transfected HEK293T cells. Animal behavior analysis showed that borneol can significantly reduce acute and chronic itch behavior in C57BL/6J mice, but this effect was eliminated in Trpa1^-/-, Trpm8^-/- mice, or at least in Trpa1^-/-/Trpm8^-/- mice. Borneol elicits TRPM8 channel induced [Ca²⁺]_i responses but inhibits AITC or SADBE-induced activation of TRPA1 channels in dorsal root ganglia neurons of WT and Trpv1^-/- mice, respectively. Furthermore, the clinical results indicated that borneol could reduce itching symptoms in patients and its efficacy is similar to that of menthol.CONCLUSIONBorneol has therapeutic effects on multiple pruritus models in mice and patients with chronic itch, and the mechanism may be through inhibiting TRPA1 and activating TRPM8.

2023-05-01·Journal of Ethnopharmacology

TRPA1 is involved in the inhibitory effect of Ke-teng-zi on allergic contact dermatitis via MAPK and JAK/STAT3 signaling pathways

Article

作者: Liu, Xinqiao ; Zhang, Man ; Zhou, Zhengfan ; Xiong, Hui ; Luo, Miao ; Zhao, Zhongqiu ; Yan, Ting ; Ju, Yankun ; Mei, Zhinan

ETHNOPHARMACOLOGICAL RELEVANCEThe seeds of Entada phaseoloides (Linn.) Merr. commonly named "Ke-teng-zi" is a traditional Chinese folk medicine and reported to treat dermatitis, spasm, and headache. However, the exact effect and the mechanism of Ke-teng-zi on the treatment of dermatitis is unclear.AIM OF THE STUDYTo elucidate the antipruritic effect and molecular mechanisms of Ke-teng-zi on the treatment of allergic contact dermatitis (ACD).MATERIALS AND METHODSThe main components of the n-butanol fraction of 70% ethanol extract from Ke-teng-zi (abbreviated as KB) were analyzed by HPLC. The chloroquine (CQ)-induced acute itch and squaraine dibutyl ester (SADBE)-induced ACD chronic itch in mice was established, and the TNF-α/IFN-γ stimulated Human keratinocytes (HaCaT) were used to evaluate the antipruritic and anti-inflammatory effects of KB. Behavioral tests, lesion scoring, and histology were also examined. The expression levels of molecules in MAPK and JAK/STAT3 pathways, the mRNA levels of chemokines and cytokines in both the skin of ACD mice and the HaCaT cells were detected by western blot and qPCR. Furthermore, whole-cell patch-clamp recordings in TRPA1-tranfected HEK293T cells were used to elucidate the effect of KB on TRPA1 channels. TRPA1 siRNA was used to evaluate the role of TRPA1 in the anti-inflammatory effect of KB in keratinocytes.RESULTSThe main compounds in KB could bind to the active sites of TRPA1 mainly through hydrogen bond and hydrophobic bond interactions. KB could inhibit the scratching behavior in CQ-induced acute itch, and the inhibitory effect of KB was blocked by TRPA1 inhibitor HC-030031. In addition, KB significantly decreased the scratching bouts of ACD mice, reduced the skin lesion scores, mast cells degranulation, and epidermal thickening, inhibited the production of inflammatory chemokines/cytokines and CGRP, and down-regulated the levels of p-ERK1/2, p-p38, and p-STAT3, compared to the ACD mice. Moreover, continuous application of KB induced the desensitization of TRPA1 channels. Also, KB inhibited the expression of p-ERK1/2, p-p38, and p-STAT3, and down-regulated the expression of inflammatory chemokines and cytokines in vitro, which were reversed by the TRPA1 siRNA.CONCLUSIONSKB alleviated the pruritus and skin inflammation in ACD mice through TRPA1 channels desensitization and down-regulation of intracellular MAPK and JAK/STAT3 signaling pathways. Our results suggested that Ke-teng-zi is a potential drug for the treatment of inflammatory skin diseases such as ACD.

2023-01-01·Frontiers in medicine

Case report: Dupilumab therapy for alopecia areata in a 4-year-old patient resistant to baricitinib.

作者: Zhuo, Jia ; Cai, Lu ; Zhao, Min ; Wei, Yi ; Lin, Mao ; Tao, Xiao

Alopecia areata (AA) is a non-scarring hair loss disorder. Alopecia totalis (AT) and alopecia universalis (AU) are the severe subtypes of AA. Age of onset before 6 years of age, disease duration of more than 1 year, and extensive alopecia involving more than 50% of the scalp (including AT or AU) suggest a poorer prognosis. Topical corticosteroids are the preferred first-line treatment for pediatric AA. While some treatments, such as intralesional corticosteroids, systemic steroids, contact immunotherapy with squaric acid dibutyl ester, and JAK inhibitors, showed efficacy in adults with AA, their safety profiles limit their use in pediatric AA patients. Dupilumab is a biologic that effectively addresses the patho-physiology of Th2 allergic diseases, and treats atopic diseases by inhibiting the helper Th2 immune axis. AA has been reported to be significantly improved with dupilumab for atopic dermatitis (AD) in children and adults. We report hair regrowth over all of the scalp, eyebrows, and eyelashes after 10 months of dupilumab therapy in a 4-year-old AU patient resistant to baricitinib.

100 项与 Squaric acid dibutyl ester(Squarex) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12223

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
变应性接触性皮炎	临床3期	美国	Massachusetts Institute of Technology	2022-09-15
唇疱疹	临床前	美国	Squarex	2018-03-10

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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


NCT03521479 (CTgov)	临床2期	唇疱疹	40	Squaric Acid Dibutyl Ester (Group A)	廠淵網鹽蓋糧選鏇糧餘(鏇網鏇鏇觸製醖遞築鹽) = 鑰淵築窪憲積衊鬱繭蓋簾醖築襯願獵艱淵鏇選 (觸齋壓鏇簾願壓糧選願, 鹹繭鏇構衊襯網遞積鏇 ~ 襯糧夢醖醖餘製夢鹽淵) 更多	-	2021-06-15
				Squaric Acid Dibutyl Ester (Group B)	廠淵網鹽蓋糧選鏇糧餘(鏇網鏇鏇觸製醖遞築鹽) = 觸糧製糧構鑰餘鏇膚簾簾醖築襯願獵艱淵鏇選 (觸齋壓鏇簾願壓糧選願, 簾廠簾壓構觸艱積網獵 ~ 襯鬱網顧選艱鹹築窪襯) 更多
NCT02965781 (CTgov)	临床1/2期	唇疱疹	139	placebo (Placebo Application (DMSO Only-No SADBE))	餘積廠遞觸艱繭繭積願(製鏇鑰餘廠鹽鹽壓襯鏇) = 壓蓋製遞糧鏇艱夢鑰積鬱顧艱鏇壓繭顧糧膚餘 (艱製鹽選獵鏇遞範繭淵, 簾醖鬱鏇網獵窪選蓋網 ~ 網醖構餘襯壓淵夢淵醖) 更多	-	2021-11-02
				SADBE (Two SADBE Applications)	餘積廠遞觸艱繭繭積願(製鏇鑰餘廠鹽鹽壓襯鏇) = 製觸遞鬱窪顧願蓋艱鏇鬱顧艱鏇壓繭顧糧膚餘 (艱製鹽選獵鏇遞範繭淵, 積糧簾蓋窪鬱鬱憲鑰積 ~ 餘構鏇餘積範鑰齋襯鑰) 更多
NCT01971385 (CTgov)	临床1期	唇疱疹	54	Squaric Acid solution (2% Squaric Acid Sensitization)	網獵鏇齋窪構艱製餘衊(淵憲鬱憲獵廠積觸製壓) = 衊憲壓繭築範餘膚鹽觸網構鹹蓋選襯觸餘壓觸 (憲鏇廠襯觸簾顧憲選網, 鏇網壓醖窪壓艱淵範衊 ~ 鹹繭願鑰齋遞憲遞餘繭)	-	2017-10-02
				Placebo solution (Placebo Solution)	網獵鏇齋窪構艱製餘衊(淵憲鬱憲獵廠積觸製壓) = 鬱鬱蓋窪夢襯蓋鹹廠鹽網構鹹蓋選襯觸餘壓觸 (憲鏇廠襯觸簾顧憲選網, 夢糧衊顧獵憲夢遞製壓 ~ 醖夢築鹹艱鹽觸糧遞願) 更多