Foreword

In recent years, the Pharmaceutical Society of Japan (PSJ) has hosted an International Symposium for Medicinal Sciences (ISMS), with pharmaceutical company researchers being encouraged to participate in the annual meeting of PSJ in order to create a close international relationship with researchers interested in the medicinal sciences. The first, second and third ISMS were held during the 135th, 136th and 137th PSJ annual meetings in Kobe, Yokohama and Sendai, respectively. The fourth ISMS, including two invited lectures by Prof. Erick M. Carreira of the Swiss Federal Institute of Technology in Zurich, and Prof. Vincent M. Rotello of the University of Massachusetts, Amherst, as well as 43 invited poster presenters, was organized during the 138th PSJ annual meeting in Kanazawa in 2018. Prof. Carreira presented a lecture about “Recent Developments in Strategies and Tactics towards Complex Secondary Metabolites Including Human-Derived Natural Products”, and Prof. Rotello introduced recent advances in the “Interfacing Nanomaterials with Biology: From Delivery of siRNA and CRISPR Machinery to Rapid Cell Phenotyping.” We also called for active contributions from invited lecturers and poster presenters during the 4th ISMS. For the Current Topics section in the Chemical and Pharmaceutical Bulletin (CPB) and Biological and Pharmaceutical Bulletin, we have assembled seventeen contributions. This issue of the CPB features three reviews, three communications and four regular articles which cover the entire drug discovery field including medicinal chemistry, pharmacology, pharmacokinetics, and regulatory sciences.

The first review, entitled “Development of a Potent Protein Degrader against Oncogenic BCR-ABL Protein”, is by Dr. Shibata, Dr. Naito, and their colleagues. In this review, the development of a Specific and Nongenetic Inhibitor of apoptosis protein [IAP]-dependent Protein Erasers (SNIPER) against BCR-ABL, including a discussion of its features and prospects for the treatment of chronic myelogenous leukemia (CML), is presented.

The second review, “The Latest Research and Development into the Antibody–Drug Conjugate, [fam-] Trastuzumab Deruxtecan (DS-8201a), for HER2 Cancer Therapy”, was contributed by Dr. Nakada and his colleagues. In this review, DS-8201 is indicated to have several innovative features: a highly potent novel payload with a high drug-to-antibody ratio, good homogeneity, a tumor-selective cleavable linker, stable linker-payload in circulation, and a short systemic half-life cytotoxic agent in vivo.

The third review, “Potential Anticancer Activity of Auranofin” by Dr. Onodera and his colleagues, focuses on the current understanding of auranofin for cancer therapy. Auranofin was initially developed more than 30 years ago as an oral therapy for rheumatoid arthritis.

“Design, Synthesis, and Biological Evaluation of a Conjugate of 5-Fluorouracil and an LSD1 Inhibitor”, the first communication by Dr. Ota, Prof. Suzuki and their colleagues, proposes a prodrug strategy for targeting cancers overexpressing lysine-specific demethylase 1 (LSD1), namely, conjugates of trans-2-phenylcyclopropylamine (PCPA, an LSD1 inhibitor) and the anticancer drug 5-fluorouracil (5-FU).

The second communication, entitled “Palladium-Catalyzed C–H Heteroarylation of 2,5-Disubstituted Imidazoles”, is by Dr. Togo, Prof. Kanai and their colleagues. In this communication, palladium-catalyzed C–H N-heteroarylation of N-protected-2,5-disubstituted imidazoles at the C4-position using N-heteroaryl halides as a coupling partner is extensively investigated.

The third communication, “Development of a Ligand Screening Tool Using Full-Length Human Peroxisome Proliferator-Activated Receptor-Expressing Cell Lines to Ameliorate Metabolic Syndrome”, is contributed by Dr. Tachibana, Prof. Doi and their colleagues. In this communication, a new cell-based screening tool using an engineered cell line for finding peroxisome proliferator-activated receptor (PPAR) ligands to ameliorate metabolic syndromes is presented.

The first regular article, “Different Degradation Mechanisms of Inhibitor of Apoptosis Proteins (IAPs) by the Specific and Nongenetic IAP-Dependent Protein Eraser (SNIPER)”, by research groups of the National Institute of Health Sciences and Takeda Pharmaceutical Co., Ltd., shows that the degradation of a cellular inhibitor of apoptosis protein 1 (cIAP1) and an X-linked inhibitor of apoptosis protein (XIAP) by SNIPER (BRD)-1 is induced via mechanisms different to those of the known SNIPER system.

In “Structure–Activity Relationship of Biakamide, Selective Growth Inhibitors under Nutrient-Starved Condition from Marine Sponge”, the second regular article, presented by Dr. Ishida, Dr. Kotoku and their colleagues, examines the structure–activity relationship (SAR) of biakamide in the creation of an easily accessible analog, and to gain insights into the participation of the substructures in growth–inhibitory activity toward the development of anticancer drugs.

The third regular article, “Bis-Heteroaryl Pyrazoles: Identification of Orally Bioavailable Inhibitors of Activin Receptor-Like Kinase-2 (R206H)”, contributed by Dr. Sekimata, Dr. Koyama and their colleagues, describes the identification of Bis-heteroaryl pyrazole as an orally bioavailable inhibitor of activating receptor-like kinase-2 closely associated with the pathogenesis of fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG).

The fourth regular article, “Spontaneously Cleavable Glycosylated Linker Capable of Extended Release of Its Conjugated Peptide”, by Dr. Ochiai, Dr. Nishiuchi and their colleagues, describes the development of a self-cleavage glycosylated linker that allows for an increase in the solubility and stability of peptides in plasma.

I believe that these reviews, communications, and articles provide useful information for progress in the medicinal sciences, and sincerely thank all authors for their significant contributions.