A multi-national, multi-centre, double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of oral soraprazan in Stargardt disease

开始日期2019-05-14

申办/合作机构-

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100 项与 Soraprazan(Takeda Pharmaceutical Co., Ltd.) 相关的转化医学

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100 项与 Soraprazan(Takeda Pharmaceutical Co., Ltd.) 相关的专利（医药）

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项与 Soraprazan(Takeda Pharmaceutical Co., Ltd.) 相关的文献（医药）

2024-03-15·ChemBioChem

Enzymatic Synthesis of Indole‐Based Imidazopyridine using α‐Amylase

Article

作者: Tyagi, Vikas ; Kamboj, Priya

AbstractThe imidazo[1,2‐a]pyridine scaffold has gained significant attention due to its presence as a lead structure in several commercially available pharmaceuticals like zolimidine, zolpidem, olprinone, soraprazan, etc. Further, indole‐based imidazo[1,2‐a]pyridine derivatives have been found interesting due to their anticancer and antibacterial activities. However, limited methods have been reported for the synthesis of indole‐based imidazo[1,2‐a]pyridines. In this study, we have successfully developed a biocatalytic process for synthesizing indole‐based imidazo[1,2‐a]pyridine derivatives using the α‐amylase enzyme catalyzed Groebke‐Blackburn‐Bienayme (GBB) multicomponent reaction of 2‐aminopyridine, indole‐3‐carboxaldehyde, and isocyanide. The generality and robustness of this protocol were shown by synthesizing differently substituted indole‐based imidazo[1,2‐a]pyridines in good isolated yields. Furthermore, to make α‐amylase a reusable catalyst for GBB multicomponent reaction, it was immobilized onto magnetic metal‐organic framework (MOF) materials [Fe3O4@MIL‐100(Fe)] and found reusable up to four consecutive catalytic cycles without the significant loss in catalytic activity.

2022-06-09·Journal of Medicinal Chemistry1区 · 医学

Structural Basis for Binding of Potassium-Competitive Acid Blockers to the Gastric Proton Pump

1区 · 医学

Article

作者: Madapally, Hridya Valia ; Abe, Kazuhiro ; Hayashida, Kenichi ; Morita, Mikio ; Shigematsu, Hideki ; Khandelia, Himanshu ; Yamagishi, Tatsuya ; Tanaka, Saki ; Oshima, Atsunori ; Gerle, Christoph

As specific inhibitors of the gastric proton pump, responsible for gastric acidification, K⁺-competitive acid blockers (P-CABs) have recently been utilized in the clinical treatment of gastric acid-related diseases in Asia. However, as these compounds have been developed based on phenotypic screening, their detailed binding poses are unknown. We show crystal and cryo-EM structures of the gastric proton pump in complex with four different P-CABs, tegoprazan, soraprazan, PF-03716556 and revaprazan, at resolutions reaching 2.8 Å. The structures describe molecular details of their interactions and are supported by functional analyses of mutations and molecular dynamics simulations. We reveal that revaprazan has a novel binding mode in which its tetrahydroisoquinoline moiety binds deep in the cation transport conduit. The mechanism of action of these P-CABs can now be evaluated at the molecular level, which will facilitate the rational development and improvement of currently available P-CABs to provide better treatment of acid-related gastrointestinal diseases.

2022-03-01·Free Radical Biology and Medicine2区 · 医学

Removal of RPE lipofuscin results in rescue from retinal degeneration in a mouse model of advanced Stargardt disease: Role of reactive oxygen species

2区 · 医学

Article

作者: Fang, Yuan ; Schraermeyer, Ulrich ; Biesemeier, Antje ; Peters, Tobias ; Szewczyk, Grzegorz ; Tschulakow, Alexander V ; Heiduschka, Peter ; Burnet, Michael ; Julien-Schraermeyer, Sylvie ; Taubitz, Tatjana ; Sarna, Tadeusz

Accumulation of lipofuscin in the retinal pigment epithelium (RPE) is a hallmark of aging and is associated with retinal degeneration encountered in age-related macular degeneration (AMD) and Stargardt disease (SD). Currently, treatment for lipofuscin-induced retinal degeneration is unavailable. Here, we report that Remofuscin (INN: soraprazan, a tetrahydropyridoether small molecule) reverses lipofuscin accumulation in aged primary human RPE cells and is non-cytotoxic in aged SD mouse RPE cells in vitro. In addition, we show that the removal of lipofuscin after a single intravitreal injection of Remofuscin results in a rescue from retinal degeneration in a mouse model of advanced SD which is even accompanied by an amelioration of the retinal dysfunction. Finally, we demonstrate that the mechanism causing lipofuscinolysis may involve the reactive oxygen species generated via the presence of Remofuscin. These data suggest a possible therapeutic approach to untreatable lipofuscin-mediated diseases like AMD, SD and lipofuscinopathies in neurodegenerative diseases.

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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
斯塔加特病	临床2期	-	Takeda Pharmaceutical Co., Ltd.	-
胃食管反流	临床前	-	Takeda Pharmaceutical Co., Ltd.	-
胃食管反流	临床前	德国	ALTANA Pharma AG	-