Overcoming Obstacles to Drug Repositioning in Japan

Nishimura, Yuhei; Tagawa, Masaaki; Ito, Hideki; Tsuruma, Kazuhiro; Hara, Hideaki

doi:10.3389/fphar.2017.00729

Cited by 9 publications

(5 citation statements)

References 48 publications

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“…However, to promote DR in Japan, three Japanese pharmaceutical companies have started joint implementation of a drug discovery program, Joint Open INnovation of drUg repositioning (JOINUS), using a drug repositioning compound library constructed by these companies in 2017 (https://open-innovation-joinus.jp/joinus/). Nishimura et al described in detail the ongoing efforts to stimulate DR in Japan . Furthermore, the re–establishment of intellectual property for repositioned drugs may solve major problems of DR for practical use in patients.…”

Section: Discussionmentioning

confidence: 99%

“…In most cases, DR can allow researchers to avoid carrying out preclinical tests and phase I trials, thereby reducing the cost of the drug development process (Figure ). Some estimates have suggested that DR requires an average of 6.5 years and US$300m dollars to approve and launch a drug …”

Section: Advantages Of Drug Repositioningmentioning

confidence: 99%

“…Currently, on average, the cost for conventional de novo discovery and development of a drug is approximately US$2.5bn and requires around 10‐15 years for the drug to reach the market . In Japan, the average time and costs to launch a drug de novo are 9.2 years and 55 billion yen, respectively . Moreover, only approximately 1 in 10 drugs entering phase I clinical trials is finally approved by the US Food and Drug Administration (FDA), and the proportion is decreased to 1 in 15 for drugs with an oncology indication in the USA …”

Section: Introductionmentioning

confidence: 99%

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Drug repositioning in cancer: The current situation in Japan

et al. 2020

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Cancer is a leading cause of death worldwide, and the incidence continues to increase. Despite major research aimed at discovering and developing novel and effective anticancer drugs, oncology drug development is a lengthy and costly process, with high attrition rates. Drug repositioning (DR, also referred to as drug repurposing), the process of finding new uses for approved noncancer drugs, has been gaining popularity in the past decade. DR has become a powerful alternative strategy for discovering and developing novel anticancer drug candidates from the existing approved drug space. Indeed, the availability of several large established libraries of clinical drugs and rapid advances in disease biology, genomics/transcriptomics/ proteomics and bioinformatics has accelerated the pace of activity-based, literaturebased and in silico DR, thereby improving safety and reducing costs. However, DR still faces financial obstacles in clinical trials, which could limit its practical use in the clinic. Here, we provide a brief review of

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Section: Discussionmentioning

confidence: 99%

Section: Advantages Of Drug Repositioningmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Drug repositioning in cancer: The current situation in Japan

et al. 2020

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“…1. Drug repositioning helps to curtail the drug development cost, which leads to an improvement in the economy of the treatment [15].…”

Section: Advantages Of Drug Repositioningmentioning

confidence: 99%

Role of Drug Repurposing in Cancer Treatment and Liposomal Approach of Drug Targeting

Galatage¹,

Manjappa²,

Waghmode³

et al. 2023

Drug Repurposing - Advances, Scopes and Opportunities in Drug Discovery

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Cancer is the leading cause of death, and incidences are increasing significantly and patients suffering from it desperately need a complete cure from it. The science of using an already-invented drug that has been approved by the FDA for a new application is known as “drug repurposing.” Currently, scientists are drawn to drug repositioning science in order to investigate existing drugs for newer therapeutic uses and cancer treatment. Because of their unique ability to target cancer cells, recently repurposed drugs and the liposomal approach are effective in the treatment of cancer. Liposomes are nanovesicles that are drastically flexible, rapidly penetrate deeper layers of cells, and enhance intracellular uptake. More importantly, liposomes are biocompatible, biodegradable; entrap both hydrophobic and hydrophilic drugs. This chapter summarizes various approaches to drug repurposing, as well as drug repurposing methods, advantages and limitations of drug repurposing, and a liposomal approach to using repurposed drugs in cancer targeting. This chapter also summarizes liposomal structure, drug loading, and the mechanism of liposomes in targeted cancer treatment. The lipid-based liposomal approach is emerging as a powerful technique for improving drug solubility, bioavailability, reducing side effects, and improving the therapeutic efficacy of repurposed drugs for cancer treatment.

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“…Because the candidate drugs have usually passed phase I safety trials, they can directly enter phase II/III safety/efficacy trials for the new indication, greatly reducing the cost and time associated with novel drug development. Drug repositioning has successfully identified therapies for various diseases, including Parkinson’s disease and dry eye [ 14 ], and has been aided by the concept of The Connectivity Map [ 15 , 16 ], which is based on the hypothesis that the mechanism of action of two drugs may be similar if they have similar gene expression signature (GES) and that a drug may be therapeutic if it elicits the opposite GES to that induced by the disease [ 17 , 18 ]. The data-driven approach has previously shown success when applied to drug repositioning [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

An Integrated In Silico and In Vivo Approach to Identify Protective Effects of Palonosetron in Cisplatin-Induced Nephrotoxicity

et al. 2020

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Cisplatin is widely used to treat various types of cancers, but it is often limited by nephrotoxicity. Here, we employed an integrated in silico and in vivo approach to identify potential treatments for cisplatin-induced nephrotoxicity (CIN). Using publicly available mouse kidney and human kidney organoid transcriptome datasets, we first identified a 208-gene expression signature for CIN and then used the bioinformatics database Cmap and Lincs Unified Environment (CLUE) to identify drugs expected to counter the expression signature for CIN. We also searched the adverse event database, Food and Drug Administration. Adverse Event Reporting System (FAERS), to identify drugs that reduce the reporting odds ratio of developing cisplatin-induced acute kidney injury. Palonosetron, a serotonin type 3 receptor (5-hydroxytryptamine receptor 3 (5-HT3R)) antagonist, was identified by both CLUE and FAERS analyses. Notably, clinical data from 103 patients treated with cisplatin for head and neck cancer revealed that palonosetron was superior to ramosetron in suppressing cisplatin-induced increases in serum creatinine and blood urea nitrogen levels. Moreover, palonosetron significantly increased the survival rate of zebrafish exposed to cisplatin but not to other 5-HT3R antagonists. These results not only suggest that palonosetron can suppress CIN but also support the use of in silico and in vivo approaches in drug repositioning studies.

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Overcoming Obstacles to Drug Repositioning in Japan

Cited by 9 publications

References 48 publications

Drug repositioning in cancer: The current situation in Japan

Drug repositioning in cancer: The current situation in Japan

Role of Drug Repurposing in Cancer Treatment and Liposomal Approach of Drug Targeting

An Integrated In Silico and In Vivo Approach to Identify Protective Effects of Palonosetron in Cisplatin-Induced Nephrotoxicity

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