Banyu Pharmaceutical Co. Ltd

Merck Sharp + Dohme Corp.

Msd K.k.

Hidehito Kotani

Kazuhiko Takahashi

Hiraku Itadani

Hiroaki Suwa

Akio Kanatani

Mark E Layton

Shigeru Tokita

Akane Ishihara

Hiroshi Hirai

Satoshi Mashiko

Hiromitsu Araki

Hiromits Araki

Nao Odagiri

Tsutomu Kobayashi

The invention relates to combination anticancer therapy with certain Akt inhibitor and other anticancer agents such as anticancer antimetabolites, anticancer antibiotics, plant-derived anticancer agents, anticancer platinum-coordinated complex compounds, anticancer camptothecin derivatives and anticancer tyrosine kinase inhibitors.

Combination cancer therapy with an AKT inhibitor and other anticancer agents

To clarify histamine receptor H3 protein function in vivo, the present inventors constructed a nonhuman higher animal in which the expression of a histamine receptor H3 gene was artificially inhibited. As a result, the present inventors found that this nonhuman higher animal showed increased body weight, food intake, blood insulin level, or blood leptin level compared with a control. Thus, the present inventors found that abnormalities in the histamine receptor H3 protein relate to diseases characterized by changes in body weight or food intake, and this has made it possible to screen drugs for treatment or prevention of these diseases, and to examine these diseases.

Utilization of histamine receptor h3 gene participating in body weight or food intake control

In the examination of obesity or leanness, the examination is based on the expression level of the MCP-1 gene or the MCP-1 protein in a tissue or cell analyte, or on the polymorphism in the gene. In the evaluation of compounds, including screening for therapeutic agents for obesity or leanness, the properties of the MCP-1 gene or the MCP-1 protein are utilized to carry out the evaluation.

Method for examining obesity or leanness

Examination of obesity or emaciation is performed based on expression levels of LCE gene or protein in a test tissue or a test cell or a polymorphism of the gene. Evaluation of compounds including screening of therapeutic agents for obesity or emaciation is performed utilizing the nature of LCE gene or protein.

Method of evaluating compound efficacious in treating obesity

Internal domain 3 of seven transmembrane G protein-coupled receptors is important for G protein binding or receptor activity, and is well conserved. In H3 receptors, which are a type of G protein-coupled receptor, this region is also conserved in the same way. Therefore, as a result of using PCR to introduce point mutations into sequences encoding the region in H3 receptor cDNA, H3 receptor mutants comprising extremely strong constitutive activity could be successfully produced. The present inventors further found that by using constitutively active H3 receptor mutants, drug candidate compounds such as H3 receptor inverse agonists can be screened more easily and efficiently.

Constitutively active histamine H3 receptor mutants and uses thereof

Growing community of inventors

Tsukuba, Japan

Hidehito Kotani