Vol.68 No.4 July 2020
History and prospects of development of antibacterial agents of Japanese origin
Kyorin Pharmaceutical Co., Ltd., 6, Kanda Surugadai 4-chome, Chiyoda-ku, Tokyo, Japan
Abstract
The discovery of penicillin by Fleming and of streptomycin by Waksman, and the development of sulfonamides by Domagk in the 20th century revolutionized the treatment of bacterial infections. The discovery of further drug classes (e.g., more drugs of the aminoglycosides, tetracyclines, cephalosporins, macrolides, glycopeptides, quinolones, carbapenems) between 1930 and 1970, the so-called "Discovery of new classes era", and the development of their derivatives by chemical modification from the 1970s to the late 1990s, the so-called "Chemical modification era", has led to widespread therapeutic use of antibacterial agents. Many antibacterial agents of Japanese origin were developed during the "Chemical modification era", contributing to the treatment of infectious diseases around the world. Consequently, antibacterial chemotherapy has become an important integral component of medical practice and contributed significantly to the health of the modern society and increase in life expectancy.
However, drug-resistant bacteria have continued to emerge and spread globally due to misuse and overuse of antimicrobials since the 1980s, and currently, antimicrobial resistance (AMR) has begun to pose a significant threat to human and animal health, and to global security and economy. AMR reduces the effectiveness of the existing antimicrobial agents against infectious diseases and actually represents a step backward in modern medicine, towards the pre-antibiotic era.
New antimicrobial agents to counter AMR are urgently needed; however, the current development pipeline is weak and not sufficient to keep up with the pace of emergence of resistance. Over the past two decades, many pharmaceutical companies, including Japanese companies, withdrew from antimicrobial R&D due to scientific challenges, as it proved difficult to discover new classes of agents and new targets, and economic challenges, namely, low returns for investments. To overcome these challenges, several push and pull incentives are currently being provided for supporting drug-discovery researches to counter AMR, reduce the clinical and regulatory burden, and extend market exclusivity in USA and Europe. The innovative incentives will become a very important strategy to stimulate antimicrobial R&D globally to counter AMR.
Recently, these incentives to facilitate and promote antimicrobial R&D have contributed to an increase in the number of approved agents and strengthening of the pipeline of new agents directed against pathogens showing AMR in the USA.
I would like to provide an overview of the contribution of antibacterial agents of Japanese origin for the control of past and present bacterial infectious diseases, and to discuss the prospects of development of new antibacterial agents in Japan.
Key word
antibacterial agent, antimicrobial resistance, drug discovery, Japan
Received
January 14, 2020
Accepted
March 18, 2020
Jpn. J. Chemother. 68 (4): 499-509, 2020
