Our activity in Chugai Pharmaceutical has been focused on discovery research, especially on biotechnology and chemical technology. To create innovative drugs and to fulfill unmet medical needs, we have established several new drug discovery platforms. We will continue such activities to keep our competitive advantage, and accelerate 3 other points, internal collaboration between research division and early-development functions, external collaboration by establishing win-win relation, and utilizing Dx effectively, to realize our new business plan （TOP I 2030）.

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The Immunology Frontier Research Center （IFReC） was established in 2007 at Osaka University under the World Premier International Research Center Initiative （WPI） of the Ministry of Education, Culture, Sports, Science and Technology （MEXT）. Using a new industry-university collaboration framework since FY2017 that guarantees IFReC researchers the freedom to pursue research based on their own interests, IFReC is further advancing basic immunology research with funding from its comprehensive collaboration agreements with two pharmaceutical companies instead of funding from the WPI program. These collaborations have made it possible for the results of IFReC’s basic research to be contributed to society through joint research with the companies. Kiyoshi Takeda, the new center director who assumed the directorship in 2019, is strongly promoting human immunology to elucidate human immune mechanisms through the use of human biological specimens with cutting-edge technologies such as single-cell analysis.

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Open innovation, which started about 7-8 years ago in Japan, is now gaining momentum, and companies are preparing teams to evaluate external projects and are making every effort to acquire new technologies and assets from external sources, both in Japan and overseas. In particular, the probability of in-house drug discovery has declined significantly, and unless a company is in the top two or three in the world in terms of the same mechanism （= Mode of Action） in the development stage, it will not be able to obtain sufficient compensation （i.e., value = sales） even if it launches a drug. Innovation can come from anywhere in the world, so how important is it to pick up on it in a timely manner? In this paper, I would like to share what we are doing and what I feel in my daily work experience, especially for young researchers in this country.

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Multidrug-resistant bacterial infections caused by Gram-negative bacteria have become a serious problem all over the world. The development of antibacterial agents with a novel mechanism of action that indicates no cross-resistance with existing antibacterial agents has been desired. UDP-3-O-acyl-N-acetylglucosamine deacetylase （LpxC） has been an attractive drug target, but has not yet reached the market as an inhibitor. Hydroxamic acid groups have been commonly used as a zinc coordination part in the major LpxC inhibitors, but the toxicity of concern based on the structure is often reported. In this study, we aimed to create a novel non-hydroxamate LpxC inhibitor with FBDD strategy. As a result, we succeeded in creating TP0586532, which is effective against carbapenem-resistant Klebsiella pneumoniae and has a low risk of cardiovascular toxicity.

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Drugs activating gonadotropin-releasing hormone （GnRH） receptor, GnRH analogs （agonists and antagonists）, have been clinically applied as therapeutic agents for sex-hormone related diseases. GnRH antagonists could be safer therapeutic agents without symptom exacerbation found in agonists. However, all previously launched GnRH antagonists were peptide drugs and were limited to injections. The development of orally available non-peptide GnRH antagonists therefore has been expected. We have previously found the thienopyrimidine compound TAK-013 based on small molecule studies focusing on the β-turn structure of GnRH. TAK-013 showed high GnRH binding affinity, but it is necessary to reduce the risk of CYP3A4 inhibition and improve in vivo activities of TAK-013. Further optimization of substituent was performed using the information of molecular modeling with GnRH receptor and considering the reduction in Log D value and molecular weight, and we finally discovered TAK-385 （Relugolix）, which has potent GnRH antagonistic in vivo activity.

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Protein ubiquitylation is an essential post-translational modification that regulates various cellular functions such as protein degradation, signal transduction, DNA repair, and protein sorting. Behind this versatile function of ubiquitylation lies the myriad structural diversity formed by a combination of 8 ubiquitin-ubiquitin linkages, chain lengths, and post-translational modifications, and functional information embedded in different ubiquitin architecture is referred to as the ubiquitin code. Elucidation of the ubiquitin code is important for understanding the pathogenic mechanism of numerous ubiquitin-related diseases and for developing chemical protein degraders such as PROTAC. Here, We review recent advances in analyzing methods of the ubiquitin chain architecture and its application for chemical degraders.

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In the world behind the mirror, there are mirror-image structures of natural chiral molecules. Can these mirror-image substances （biomolecules and natural products） provide potential drug leads? A number of screenings using mirror-image target proteins （D-proteins） have been carried out to investigate the bioactivities of previously unexplored mirror-image substances. The present article briefly summarizes the history of this research and recent progress in the field.

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Chem-Station is a long-standing chemistry website that has been in operation for more than 20 years. As a media specializing in chemistry, it has been publishing article-based content on everything from familiar chemistry to cutting-edge research. In the wake of the spread of the COVID-19, it has also started providing video contents such as virtual symposiums. In this report, we introduce the recent operation and management of the website and its future prospects.

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