Most of universities in Japan have been annoyed by inadequate and decreasing funding by Government. Ministry of Education, Culture, Sports, Science and Technology has started new funding for universities to establish Institute of Open Innovation (IOI). IOI is expected to enhance the investment in universities by companies and thereby they will be more independent in future. Tokyo Medical and Dental University (TMDU) was among 8 universities selected to receive the funding and IOI of TMDU rolled out in December 2018. Since the concept and mission of IOI are quite new to TMDU, almost all staff have been recruited from outside. As IOI of TMDU has worked, we are introducing new rules and arrangements in TMDU to let it go forward. There remain some issues how to set a rational amount of research fund and overhead, however, we keep on challenging to evolve IOI to bring us unprecedented values.

In the past 25 years, the drug discovery research and development (R&D) model has undergone dramatic changes. The major drivers of this transformation have been discussed at length in the literature. Initially, large pharmaceutical companies tried to fill their pipelines through mergers, but this rarely increased the output of new molecular entities. On the contrary, these mergers frequently had a negative effect on research productivity. This wave of mergers of pharma companies was followed by closures of R&D centers worldwide. As pharmaceutical companies continue to explore new ways to supplement their internal pipeline, they have started to look at earlier stage assets generated by third parties. To support these activities, venture capital firms entered the fray, paving the way for a new era of transformation that is often referred to as open innovation (OI). In this article, we review how this OI model operates.

In recent years, the environment surrounding drug development has undergone remarkable changes, and diversification of new treatment technologies (modalities) due to the depletion of target molecules of disease onset for blockbuster creation or the rise of unmet medical needs. In particular, it is important to efficiently deliver new modalities (peptides or gene/nucleic acids etc.) to target sites (organs, tissues, cells, etc.). To enable them, it is necessary to use the DDS. Especially with the progress of super aging, the development of new DDS technology for the treatment of Alzheimer’s disease, neurological diseases, cancer, etc. is expected to lead to the realization of drug discovery.

RNA interference (RNAi) therapeutic, a nucleic acid medicine that can downregulate the target-gene expression specifically, attracts a great deal of attention more than ever, because of the market of patisiran (Onpattro^®) in 2018, a first RNAi drug in the world. We recently developed a novel RNAi therapeutic for intracoelomic injection. A coelomic cavity, including pleural cavity and peritoneal cavity, is a common site for the development of several refractory cancers, e.g. malignant pleural mesothelioma and peritoneal disseminated metastasis for cancer, which is poorly responsive to conventional systemic chemotherapy. In this topic, we review the therapeutic efficacy of our intracoelomic RNAi therapeutic (DFP-10825) for the treatment of refractory cancers developed in coelomic cavity.

To gain the potential of drug candidates for treatment of central nervous system disorders such as Alzheimer’s disease, the methods to efficiently deliver them into the brain parenchyma have to be established. Recently, intranasal administration has been recognized as an attractive route to deliver drugs to the brain by bypassing blood-brain barrier (BBB), and currently called as “nose-to-brain delivery”. In this essay, we describe the proposed mechanisms related to direct transport of drugs from nasal cavity to brain parenchyma. The nose-to-brain transport of drugs can be significantly prevented by the physical and biological factors in nasal mucosa, thus we summarize the recent studies challenging to enhance the efficiency of the nose-to-brain delivery. We further explain our strategy to increase the nose-to-brain delivery of peptide drugs by physically mixing with the cell-penetrating peptides (CPPs).

mRNA and small RNAs (siRNA and miRNA) are attractive modalities for cure of diseases by complementation and knockdown of proteins. To exhibit their own functions, a Drug Delivery System (DDS) is required to deliver them to the target cells, overcome the biological membranes, and release them into the cytoplasm. As a material for nucleic acid delivery, we developed a lipid-like material (ssPalm) that breaks through biological membranes by positively charging in response to acidic environment, and self-disintegrates in response to cytoplasmic reducing environment. This paper outlines the design concept of this material and gives examples of molecular modifications tailored to the medical application.

Exosomes (extracellular vesicles) are small membrane vesicles (30-200 nm) secreted by various cell types with encapsulation of bioactive molecules (e.g. microRNA and enzymes). Exosomes are highly expected to be next generation drug delivery tools owing to their pharmaceutical advantages. In order to be utilized for receptor-targeted delivery based on exosomes, development of functionalized exosomes, which can recognize specific receptors and induce cellular exosomal uptake, should be needed. In this review, I introduce a novel technique for effectively targeting receptors, using artificial leucine zipper peptides that form heterodimeric coiled-coils.

Discovery of CNS penetrant HDAC inhibitors has attracted medicinal chemists’ attentions because inhibition of HDAC in CNS is a potent treatment of neurodegenerative diseases such as Alzheimer’s disease. We designed and synthesized a pyrilamine derivative 1 as a selective class I HDAC inhibitor focusing on pyrilamine-sensitive proton-coupled organic cation antiporter (PYSOCA) expressed at the blood brain barrier (BBB). Synthesized compound 1 inhibited class I HDACs selectively and our BBB transport study showed that compound 1 is a substrate of PYSOCA. In addition, compound 1 showed higher BBB permeability than CI-994 in rats.

12th Asian Federation for Medicinal Chemistry (AFMC) International Medicinal Chemistry Symposium (AIMECS 2019) was held in Istanbul, Turkey on September 8–11, 2019. The theme of this meeting was “New Avenues for Design and Development of Translational Medicine”. Twelve keynote lectures, 30 oral presentations and 58 poster presentations were given. In this report, outlines of the meeting are described