Takeda Pharmaceutical Company Limited

Takeda Chemical Industries, Inc.

Yasuaki Ito

Shuji Hinuma

Ryo Fujii

Masataka Harada

Makoto Kobayashi

Shoichi Ohkubo

Tsuneo Yasuma

Hideyuki Tanaka

Nobuhiro Suzuki

Masaki Hosoya

Kazunori Nishi

Shoji Fukusumi

Shinobu Sasaki

Kazuhiro Ogi

Yuji Kawamata

Tadatoshi Hashimoto

Kohji Fukatsu

Hideki Kizawa

Yasuhiro Tanaka

Makoto c/o Takeda Pharm Co Ltd Kobayashi

Tadatoshi c/o Takeda Pharm Co Ltd Hashimoto

By using a G protein-coupled receptor protein comprising an amino acid sequence, which is the same or substantially the same as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, and an ionizable metal element or a salt thereof, an agonist for or an antagonist to the above receptor protein or a salt thereof can be efficiently screened.

Screening method for binding property or signal transduction alterations

The GPR40 receptor function regulator of the present invention, which comprises a compound having an aromatic ring and a group capable of releasing cation is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

Receptor function regulator

The present invention provides a method of screening a compound or its salt that alters binding properties of a protein comprising the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1, or a salt thereof, and a ligand capable of specifically binding to the protein or its salt, which comprises using (a) the protein, its partial peptide, or a salt thereof and (b) the ligand; a screening kit therefor, and so on. The screening method and kit of the present invention are useful for screening an agent for the prevention/treatment of, e.g., digestive tract disorders, cancer, immune disorders, type II diabetes mellitus or obesity, etc.

Screening method

By using (1) a G protein-coupled receptor protein having the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1 or its salt and (2) a fatty acid or an eicosanoid, a compound or its salt that can change the binding properties of the receptor protein or its salt to the fatty acid or the eicosanoid can be screened efficiently.

DNA primers effective in screening G protein coupled receptor protein-encoding DNA fragments are provided. The primers which are complementary to nucleotide sequences that are in community with (homologous to) the nucleotide sequences encoding amino acid sequences corresponding to or near the first membrane-spanning domain or the sixth membrane-spanning domain each of known various G protein coupled receptor proteins were designed and synthesized. Methods of amplifying G protein coupled receptor protein-encoding DNAs using the above DNA primers, and novel target G protein coupled receptor protein-encoding DNAs are also provided. Screening of DNA libraries can be efficiently carried out. Human pituitary gland or amygdala-derived and mouse pancreas-derived G protein coupled receptor proteins, etc. or salts thereof, partial peptides thereof, DNAs coding for the above G protein coupled receptor proteins, processes for producing the above G protein coupled receptor proteins, methods of determining ligands for the above G protein coupled receptor proteins, methods of screening compounds that inhibit the binding between the ligand and the G protein coupled receptor proteins or screening kits therefor, compounds or salts thereof obtained by the above screening method or the screening kit, pharmaceutical compositions containing the above compounds or salts thereof, and antibodies against the above protein coupled receptor proteins or partial peptides thereof are provided.

G protein coupled receptor protein production, and use thereof

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Tsukuba, Japan

Yasuaki Ito