A Phase 1, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of Topical SM04755 Solution Following Topical Administration to Subjects with Mild to Moderate Plaque Psoriasis

开始日期2017-10-09

申办/合作机构-

NCT03502434 / Completed临床1期

A Phase 1, Single-Center, Repeat Insult Patch Test (RIPT) Study Evaluating the Sensitization Potential of Topical SM04755 Solution

This is a single center, randomized, controlled, within subject comparison, single dose study to determine the sensitization potential of SM04755 solution on normal skin under semi-occlusive patch conditions.

开始日期2017-09-11

申办/合作机构

Biosplice Therapeutics, Inc.

NCT03229291 / Completed临床1期

A Phase 1, Single-Center, Randomized, Single-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of SM04755 Following Topical Administration to Healthy Subjects

This study is a single-center, randomized, single-blind, placebo-controlled, multiple ascending dose study of SM04755 solution applied topically once daily for 14 days to intact skin overlying the inner thigh of healthy subjects at an estimated body surface area (BSA) of 80 cm^2. Dosing cohorts will consist of 8 subjects who will be randomized 3:1 (SM04755:placebo).

开始日期2016-11-03

申办/合作机构

Biosplice Therapeutics, Inc.

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100 项与 Teplinovivint 相关的转化医学

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100 项与 Teplinovivint 相关的专利（医药）

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项与 Teplinovivint 相关的文献（医药）

2021-09-01·Journal of Orthopaedic Research3区 · 医学

SM04755, a small‐molecule inhibitor of the Wnt pathway, as a potential topical treatment for tendinopathy

3区 · 医学

Article

作者: Ghias, Abdullah ; Deshmukh, Vishal ; O'Green, Alyssa L. ; Hood, John ; Yazici, Yusuf ; Barroga, Charlene ; Ibanez, Maureen ; KC, Sunil ; Hofilena, Brian ; Seo, Tim ; Kennedy, Sarah ; Dellamary, Luis ; Chiu, Kevin ; Tambiah, Jeyanesh ; Stewart, Joshua

AbstractThe Wnt pathway is upregulated in tendinopathy, affecting inflammation and tenocyte differentiation. Given its potential role in tendinopathy, this signaling pathway may be a relevant target for treatment. The current study examined the therapeutic potential of SM04755, a topical, small‐molecule Wnt pathway inhibitor, for the treatment of tendinopathy using in vitro assays and animal models. In vitro, SM04755 decreased Wnt pathway activity, induced tenocyte differentiation, and inhibited catabolic enzymes and pro‐inflammatory cytokines in human mesenchymal stem cells, rat tendon‐derived stem cells, and human peripheral blood mononuclear cells. Evaluation of the mechanism of action of SM04755 by biochemical profiling and computational modeling identified CDC‐like kinase 2 (CLK2) and dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A) as molecular targets. CLK and DYRK1A inhibition by siRNA knockdown or pharmacological inhibition induced tenocyte differentiation and reduced tenocyte catabolism. In vivo, topically applied SM04755 showed therapeutically relevant exposure in tendons with low systemic exposure and no detectable toxicity in rats. Moreover, SM04755 showed reduced tendon inflammation and evidence of tendon regeneration, decreased pain, and improved weight‐bearing function in rat collagenase‐induced tendinopathy models compared with vehicle control. Together, these data demonstrate that CLK2 and DYRK1A inhibition by SM04755 resulted in Wnt pathway inhibition, enhanced tenocyte differentiation and protection, and reduced inflammation. SM04755 has the potential to benefit symptoms and modify disease processes in tendinopathy.

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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
肌腱病	临床1期	美国	Biosplice Therapeutics, Inc.	2016-11-03
结直肠癌	临床1期	美国	Biosplice Therapeutics, Inc.	2014-06-19
肝癌	临床1期	美国	Biosplice Therapeutics, Inc.	2014-06-19
胰腺癌	临床1期	美国	Biosplice Therapeutics, Inc.	2014-06-19
胃癌	临床1期	美国	Biosplice Therapeutics, Inc.	2014-06-19
系统性硬皮病	临床1期	美国	Biosplice Therapeutics, Inc.	-

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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


EULAR2018	N/A	银屑病	-	SM04755	(範廠憲夢廠觸鑰範衊製) = 鏇築顧積獵窪醖壓蓋憲窪簾積鹽鹽製襯製齋選 (窪築願顧淵淵積餘艱願 ) 更多	积极	2018-06-13
EULAR2018	N/A	银屑病	-	Vehicle	(範廠憲夢廠觸鑰範衊製) = 壓鹽顧鬱鏇艱蓋網網繭窪簾積鹽鹽製襯製齋選 (窪築願顧淵淵積餘艱願 ) 更多	积极	2018-06-13
ACR2016	N/A	肌腱病	-	SM04755	糧糧齋襯觸淵艱蓋鏇襯(顧鹹鏇製願構憲蓋蓋積) = 夢壓鑰製鬱壓艱夢築醖窪顧獵廠繭餘壓獵艱壓 (夢艱膚鏇範鹽顧網齋遞 )	积极	2016-11-14