KUS-121(KUS-121) - 药物靶点：VCP_在研适应症：视网膜动脉闭塞，视网膜静脉阻塞_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

VCP

作用机制

VCP抑制剂(Transitional endoplasmic reticulum ATPase inhibitors)

治疗领域

心血管疾病眼部疾病

在研适应症

视网膜动脉闭塞视网膜静脉阻塞

非在研适应症-

原研机构

Kyoto University

在研机构

Kyoto Drug Discovery & Development Co., Ltd.初创企业

Kyoto University

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C22H17FN4O3S

InChIKeyQOLHSSNEBRFIEQ-UHFFFAOYSA-N

CAS号1357245-09-0

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关联

2

项与 KUS-121 相关的临床试验

NCT06178055 / Recruiting临床2期

A Phase 2, Double-masked, Randomized, Sham-controlled, Multiple-dose Study of the Efficacy and Safety of Intravitreal KUS121 in the Treatment of Non-Arteritic Central Retinal Artery Occlusion (CRAO)

Central retinal artery occlusion (CRAO) is an ophthalmologic emergency which leads to severe and permanent vision loss. There is no evidence-based therapy for CRAO. The objective of this GION study is to evaluate the efficacy and safety of KUS121 intravitreal (IVT) injection in participants with acute non-arteritic CRAO.

开始日期2024-04-16

申办/合作机构

Kyoto Drug Discovery & Development Co., Ltd.初创企业

JPRN-UMIN000023979 / Completed临床1/2期IIT

Phase 1/2 clinical trial to evaluate the safety and efficacy of daily intravitreal injections of KUS121 for three days in patients with non-arteritic central retinal artery occlusion - Phase 1/2 clinical trial of intravitreal injections of KUS121 in patients with central retinal artery occlusion

开始日期2016-10-28

申办/合作机构-

100 项与 KUS-121 相关的临床结果

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100 项与 KUS-121 相关的转化医学

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100 项与 KUS-121 相关的专利（医药）

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15

项与 KUS-121 相关的文献（医药）

2024-01-01·Biomedicine & Pharmacotherapy

KUS121, a VCP modulator, has an ameliorating effect on acute and chronic heart failure without calcium loading via maintenance of intracellular ATP levels

Article

作者: Sowa, Naoya ; Yamasaki, Tomohiro ; Horie, Takahiro ; Matsushita, Kazuki ; Tsuji, Shuhei ; Ono, Koh ; Imai, Hirohiko ; Suzuki, Keita ; Kimura, Takeshi ; Xu, Sijia ; Otani, Chiharu ; Kakizuka, Akira ; Zou, Fuquan ; Hasegawa, Koji ; Ide, Yuya ; Kashiwa, Asami ; Kume, Eitaro ; Watanabe, Shin ; Makiyama, Takeru ; Baba, Osamu ; Nakashima, Yasuhiro

AIMSAs heart failure (HF) progresses, ATP levels in myocardial cells decrease, and myocardial contractility also decreases. Inotropic drugs improve myocardial contractility but increase ATP consumption, leading to poor prognosis. Kyoto University Substance 121 (KUS121) is known to selectively inhibit the ATPase activity of valosin-containing protein, maintain cellular ATP levels, and manifest cytoprotective effects in several pathological conditions. The aim of this study is to determine the therapeutic effect of KUS121 on HF models.METHODS AND RESULTSCultured cell, mouse, and canine models of HF were used to examine the therapeutic effects of KUS121. The mechanism of action of KUS121 was also examined. Administration of KUS121 to a transverse aortic constriction (TAC)-induced mouse model of HF rapidly improved the left ventricular ejection fraction and improved the creatine phosphate/ATP ratio. In a canine model of high frequency-paced HF, administration of KUS121 also improved left ventricular contractility and decreased left ventricular end-diastolic pressure without increasing the heart rate. Long-term administration of KUS121 to a TAC-induced mouse model of HF suppressed cardiac hypertrophy and fibrosis. In H9C2 cells, KUS121 reduced ER stress. Finally, in experiments using primary cultured cardiomyocytes, KUS121 improved contractility and diastolic capacity without changing peak Ca²⁺ levels or contraction time. These effects were not accompanied by an increase in cyclic adenosine monophosphate or phosphorylation of phospholamban and ryanodine receptors.CONCLUSIONSKUS121 ameliorated HF by a mechanism totally different from that of conventional catecholamines. We propose that KUS121 is a promising new option for the treatment of HF.

2022-05-01·American Journal of Physiology-Renal Physiology3区 · 医学

A novel VCP modulator KUS121 exerts renoprotective effects in ischemia-reperfusion injury with retaining ATP and restoring ERAD-processing capacity

3区 · 医学

Article

作者: Date, Ryosuke ; Ikeda, Hanako Ohashi ; Kakizoe, Yutaka ; Mizumoto, Teruhiko ; Kanki, Tomoko ; Hata, Yusuke ; Umemoto, Shuro ; Mukoyama, Masashi ; Izumi, Yuichiro ; Kuwabara, Takashige ; Nishiguchi, Yoshihiko ; Hayata, Manabu ; Kakizuka, Akira ; Fujimoto, Daisuke

Novel findings of this study are as follows: 1) Kyoto University substance 121 (KUS121), a novel valosin-containing protein (VCP) modulator, can reduce ATP consumption of VCP; 2) KUS121 reduced endoplasmic reticulum (ER) stress and improved cell viability in proximal tubular cells; 3) KUS121 exerted renoprotective effects against ischemia-reperfusion injury; and 4) KUS121 may prevent ischemic acute kidney injury with ATP retention and restoring ER-associated degradation capacity.

2019-10-01·JACC: Basic to Translational Science2区 · 医学

Cardioprotective Effects of VCP Modulator KUS121 in Murine and Porcine Models of Myocardial Infarction

2区 · 医学

ArticleOA

作者: Otani, Chiharu ; Kuwabara, Yasuhide ; Xu, Sijia ; Nishino, Tomohiro ; Nakazeki, Fumiko ; Ide, Yuya ; Miyasaka, Yui ; Nishiga, Masataka ; Nishi, Hitoo ; Kimura, Takeshi ; Nakao, Tetsushi ; Yamamoto, Masamichi ; Horie, Takahiro ; Tsuji, Shuhei ; Rodriguez, Randolph Ruiz ; Saito, Naritatsu ; Yanagita, Motoko ; Watanabe, Shin ; Yamasaki, Tomohiro ; Kakizuka, Akira ; Watanabe, Toshimitsu ; Nakashima, Yasuhiro ; Koyama, Satoshi ; Kimura, Masahiro ; Ono, Koh

No effective treatment is yet available to reduce infarct size and improve clinical outcomes after acute myocardial infarction by enhancing early reperfusion therapy using primary percutaneous coronary intervention. The study showed that Kyoto University Substance 121 (KUS121) reduced endoplasmic reticulum stress, maintained adenosine triphosphate levels, and ameliorated the infarct size in a murine cardiac ischemia and reperfusion injury model. The study confirmed the cardioprotective effect of KUS121 in a porcine ischemia and reperfusion injury model. These findings confirmed that KUS121 is a promising novel therapeutic agent for myocardial infarction in conjunction with primary percutaneous coronary intervention.

100 项与 KUS-121 相关的药物交易

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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
视网膜动脉闭塞	临床2期	美国	Kyoto Drug Discovery & Development Co., Ltd.初创企业	2024-04-16
视网膜静脉阻塞	临床2期	-	Kyoto University	-