ABSTRACT
Twenty years after the concept of open innovation was first proposed, entrepreneurship and horizontal division of labor have become popular in Japan, following the global trend. However, in the life science field, the foundation for open innovation is still in its infancy due to the high degree of specialization, large scale of required investment, and low probability of success. For the five years since its opening in 2018, Shonan Health Innovation Park (Shonan iPark) has taken on the challenge of building an ecosystem to create a place where a diverse range of players can realize open innovation. The key points of the efforts are the multifaceted approach taken by the governing body, which is well versed in life sciences, and on the other hand, the fostering of a mutually supportive mechanism and culture by actively borrowing the strength of the community's constituent members. In this article, we introduce the efforts to support diverse players, including venture companies, from the perspective of a science park that creates a place for open innovation.
Subject(s)
Ecosystem , JapanABSTRACT
The synthesis and biological evaluation of a series of novel 3-phenylpiperidine-4-carboxamide derivatives are described. These compounds are generated by hybridization of the substructures from two types of tachykinin NK(1) receptor antagonists. Compound 42 showed high metabolic stability and excellent efficacy in the guinea-pig GR-73637-induced locomotive activity assay at 1 and 24h after oral administration. It also exhibited good pharmacokinetic profiles in four animal species, and a low potential in a pregnane X receptor induction assay.
Subject(s)
Amides/chemistry , Amides/pharmacology , Cytochrome P-450 CYP3A/metabolism , Neurokinin-1 Receptor Antagonists , Piperidines/chemistry , Administration, Oral , Amides/chemical synthesis , Amides/pharmacokinetics , Animals , Enzyme Activation/drug effects , Guinea Pigs , Humans , Microsomes/metabolism , Motor Activity/drug effects , Piperidines/chemical synthesis , Piperidines/pharmacokinetics , Pregnane X Receptor , Receptors, Neurokinin-1/metabolism , Receptors, Steroid/metabolism , StereoisomerismABSTRACT
Kaempferol is one of the most commonly found dietary flavonoids. The exposure to kaempferol is known to inhibit degranulation from mast cells, but the inhibitory mechanism of degranulation has not been clarified yet. In this study, we investigated the involvement of heme oxygenase (HO)-1 in the anti-allergic action of kaempferol against degranulation in rat basophilic leukemia (RBL-2H3) cells. Our results demonstrate upregulation of HO enzymatic activity after short (15 min) exposure to kaempferol, followed by the induction of HO-1 expression in protein. The involvement of HO-1 in the kaempferol-induced inhibition of degranulation was confirmed using tin protoporphyrin IX (SnPP), a HO-1 inhibitor. These findings strongly suggest that kaempferol exerts anti-allergic actions via activation of the HO-1.
