Delving into the Latest Updates on KUS-121 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

VCP

Mechanism

VCP inhibitors(Transitional endoplasmic reticulum ATPase inhibitors)

Therapeutic Areas

Cardiovascular DiseasesEye Diseases

Active Indication

Retinal Artery OcclusionRetinal Vein Occlusion

Inactive Indication-

Originator Organization

Kyoto University

Active Organization

Kyoto Drug Discovery & Development Co., Ltd.Startup

Kyoto University

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC22H17FN4O3S

InChIKeyQOLHSSNEBRFIEQ-UHFFFAOYSA-N

CAS Registry1357245-09-0

View All Structures (2)

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.

Start Date16 Apr 2024

Sponsor / Collaborator

Kyoto Drug Discovery & Development Co., Ltd.Startup

JPRN-UMIN000023979 / CompletedPhase 1/2IIT

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

Start Date28 Oct 2016

Sponsor / Collaborator-

100 Clinical Results associated with KUS-121

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100 Translational Medicine associated with KUS-121

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100 Patents (Medical) associated with KUS-121

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15

Literatures (Medical) associated with KUS-121

01 Jan 2024·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

Author: 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.

01 May 2022·American Journal of Physiology-Renal PhysiologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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.

01 Oct 2019·JACC: Basic to Translational ScienceQ2 · MEDICINE

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

Q2 · MEDICINE

ArticleOA

Author: 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 Deals associated with KUS-121

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