Foreword

There has been a remarkable diversification of drug discovery modalities in recent years. In addition to conventional small-molecule drugs, antibody drugs, antibody-drug conjugates, nucleic acid drugs, mid-molecule drugs such as peptides, and PROTACs are being developed. AI-based drug discovery is also flourishing. Many of these new drug discovery modalities originated in academia and have been developed by pharmaceutical companies. Since the diversification of drug discovery modalities is attracting much attention, further development of medicinal chemistry in academia is expected. In this edition of Current Topics, entitled “Advanced Medicinal Chemistry in Academia,” young medicinal chemists, who are actively working in academia, have contributed review/original articles.

The review article entitled, “Targeted Therapy for Prostate Cancer by Prostate-Specific Membrane Antigen-Targeted Small-Molecule Drug Conjugates” by Dr. Ryo Nakajima (Graduate School of Biomedical and Health Sciences, Hiroshima University) summarizes small-molecule drug conjugates that target prostate-specific membrane antigen for the treatment of prostate cancer.¹⁾ The first regular article by Dr. Takashi Osawa and Prof. Satoshi Obika (Graduate School of Pharmaceutical Sciences, Osaka University) was entitled, “Synthesis of Coumarin-Conjugated Oligonucleotides via Knoevenagel Condensation to Prepare an Oligonucleotide Library.” They developed a new synthetic method for preparing a DNA-encoded library possessing coumarin derivatives.²⁾ The second regular article entitled, “Rational Design of Amphipathic Antimicrobial Peptides with Alternating L-/D-Amino Acids That Form Helical Structures” by Dr. Hidetomo Yokoo (National Institute of Health Sciences) and colleagues describes the design and synthesis of Stripe-based Amphipathic peptides that show improved antimicrobial activity.³⁾ The third regular article entitled, “A Structure–Activity Relationship Study of SNAIL1 Peptides as Inhibitors of Lysine-Specific Demethylase 1” by Dr. Yuri Takada (SANKEN, Osaka University) et al. describes the identification of a potent lysine-specific demethylase 1 inhibitor based on SNAIL1 peptides.⁴⁾ The fourth regular article by Dr. Shusuke Tomoshige and colleagues (Graduate School of Life Sciences, Tohoku University) was entitled, “Allosteric Hsp70 Modulator YM-1 Induces Degradation of BRD4.” They found that YM-1, an allosteric modulator of Hsp70, decreases the level of the cancer-associated protein BRD4 in cancer cells, suggesting that regulation of Hsp70 has the potential to be a promising therapeutic strategy for cancer.⁵⁾ The fifth regular article entitled, “In Silico Prediction of N-Nitrosamine Formation Pathways of Pharmaceutical Products” by Dr. Genichiro Tsuji, Dr. Yosuke Demizu (National Institute of Health Sciences), and colleagues describes the development of a risk assessment method for the formation of N-nitrosamines in pharmaceutical products.⁶⁾ The final regular article by Dr. Yasunobu Yamashita (SANKEN, Osaka University) and colleagues was entitled, “Identification of a Histone Deacetylase 8 Inhibitor through Drug Screenings Based on Machine Learning.” They expanded the chemical space for histone deacetylase 8 (HDAC8) inhibitors and identified a non-hydroxamate compound as a novel HDAC8-Selective inhibitor using machine learning.⁷⁾

I believe that this edition of Current Topics offers valuable information about novel medicinal chemistry approaches, which will significantly contribute to drug development. I also sincerely appreciate the important contributions of all the authors.

References

• 1) Nakajima R., Chem. Pharm. Bull. 72, 136–142 (2024).
• 2) Osawa T., Obika S., Chem. Pharm. Bull. 72, 143–148 (2024).
• 3) Hirano M., Yokoo H., Ohoka N., Ito T., Misawa T., Oba M., Inoue T., Demizu Y., Chem. Pharm. Bull. 72, 149–154 (2024).
• 4) Takada Y., Adachi K., Fujinaga Y., Yamashita Y., Itoh Y., Suzuki T., Chem. Pharm. Bull. 72, 155–160 (2024).
• 5) Mishima Y., Tomoshige S., Sato S., Ishikawa M., Chem. Pharm. Bull. 72, 161–165 (2024).
• 6) Tsuji G., Kurohara T., Shoda T., Yokoo H., Ito T., Masada S., Uchiyama N., Yamamoto E., Demizu Y., Chem. Pharm. Bull. 72, 166–172 (2024).
• 7) Nurani A., Yamashita Y., Taki Y., Takada Y., Itoh Y., Suzuki T., Chem. Pharm. Bull. 72, 173–178 (2024).