Zebrafish-based drug discovery has become a potential strategy by its high throughput quantitative in vivo screening and has already succeeded in several examples of phenotype-based drug discovery and personalized medicine.

Pharmaceutical companies consider open innovation as an important strategy in response to the rapidly changing R&D environment. In recent years, global pharmaceutical companies have established a new department to specialize in open innovation. In the case of Pfizer, External R&D Innovation (ERDI) and Japan Open Innovation Network (JOIN) are cooperatively working to identify innovative science and collaboration opportunities in Japan. Partnership based on mutual benefit is indispensable for open innovation and research collaboration. To succeed drug R&D despite low probability of success and make a drug originated from Japan, open innovation beyond the boundary between domestic and global companies or between academia and industry will become more necessarily.

Mechanism of development and progression of cancer has been elucidated at a molecular level by progress of recent cancer research, and the new findings lead to the research and development of novel molecular targeted drugs. This special feature provides the latest trend in cancer research for developing new molecular targeted drugs from three specialized research fields such as tumor growth and angiogenesis, cancer stem cell, and cancer immunology.

Lenvatinib mesilate is an orally-administered tyrosine kinase receptor inhibitor. Lenvatinib was discovered by Eisai Tsukuba Labs. Lenvatinib inhibits the tyrosine kinase activity of vascular endothelial growth factor receptors (VEGFR) 1–3, fibroblast growth factor receptors (FGFR) 1–4, which are involved in tumor angiogenesis, and the rearranged during transfection (RET) proto-oncogene which is involved in cancer cell proliferation. Lenvatinib binds to VEGFR2 through a novel binding mode (type V) that differs from that with conventional tyrosine kinase inhibitors. Lenvatinib inhibited VEGF- and FGF-driven angiogenesis in vitro, while administration of lenvatinib to model mice transplanted with various human cancer cells resulted in dose-dependent antitumor effects. Cell proliferation has been observed in thyroid cancer cells with FGFR overexpression or mutations in RET, suggesting that lenvatinib may exert antitumor effects by inhibiting both angiogenesis due to VEGFR and FGFR and abnormal proliferation of thyroid cancer cells due to FGFR and RET.

Cancer tissue is composed of heterogeneous cell populations which are originated from cancer stem cell, a top of the hierarchical structure. The cancer stem cell is resistant to various therapies and is the origin of a recurrence and the metastasis. Thus, it is necessary to elucidate the resistant mechanism of the cancer stem cell and to eliminate them. In this report, we describe the development of a novel therapeutic strategy targeting cancer stem cells of the solid tumors

Nivolumab (recombinant) is a human anti-human PD-1 antibody. Nivolumab is a new immune checkpoint inhibitor which was launched for the treatment of unresectable melanoma in September 2014 in Japan ahead of the rest of the world. Nivolumab inhibits the binding of PD-1 to PD-1 ligands and shows the antitumor effect by enhancing the proliferation, activation and cytotoxic activity against tumor cells, of antigen-specific T cells. The efficacy, safety, and tolerability of nivolumab were confirmed in a phase II study in Japan in the patients with malignant melanoma, proving that nivolumab is a useful therapeutic drug for malignant melanoma. Based on these results, we filed an application for a manufacturing and marketing approval in December 2013, and nivolumab received an approval as the world’s first anti-PD-1 antibody in July 2014.

In the history of therapeutic agent for acid-related diseases, more potent and longer-lasting acid suppressants have been desired. Although proton pump inhibitors (PPIs) are currently the first choice for the treatment of acid-related diseases, several points of improvement have been required.

Therefore, we started to study from 2003 aiming at the development of a new antisecretory agent which conquers several shortcomings of lansoprazole which is one of PPIs. As a result, we have succeeded in identifying TAK-438 (vonoprazan fumarate) as a novel potassium-competitive acid blocker (P-CAB), which exerts a longer and stronger effect than lansoprazole. TAK-438 was newly launched in February 2015 as Takecab^®. This new medicine might contribute to unmet medical needs of acid-related diseases as a new treatment option.

The “antedrug” or “soft” drug have been designed to exert their desired effect locally but these drugs are inactivated in the circulation to reduce unwanted systemic effects. The ideal antedrug should combine stability in the target tissue with very rapid inactivation into predictable metabolite in the systemic circulation. The metabolic consideration should be an integral part of the drug design process and that this process should focus not on improving activity alone, but also on improving the therapeutic index. Here, the concept of “antedrug” and “soft” drug has been explained and then metabolic enzymes for rapid inactivation and their species difference were shown. Finally, the several examples of “antedrug” and “soft” drug were presented according to the different approach for the design of antedrug.

51st Rencontres Internationales de Chimie Therapeutique (RICT2015) is the annual international conference in France organized by The French Medicinal Chemistry Society. The scientists focused on their researches in terms of understanding targets and mechanisms or drug discovery and selection. Sessions were roughly classified three categories: chemical biology with tool compounds, technologies for drug discovery and drug targets, and diseases. As regards medicinal chemistry, many success stories by structure-based drug discovery were reported.

ISOM (International Symposium on Olefin Metathesis and Related Chemisty) is a biennial international symposium and the 21st event was held this year in Graz, Austria, between July 12 and 16. The symposium venue was Graz University of Technology (GUT), which was located near the city center, and Professor Franz Stelzer of GUT served as the symposium chair. The symposium attracted ca. 150 participants worldwide and 6 plenary lectures (including the lectures given by the two Novel laureates, Professor Richard R. Schrock and Professor Robert H. Grubbs), 26 invited lectures, 24 general oral presentations, and 59 poster presentations were given. Next symposium will be held in 2017 in Zürich with Professor Christophe Copéret of ETH Zürich as a chairman.