Chugai Seiyaku Kabushiki Kaisha

Kaken Pharmaceutical Company, Ltd.

Atsushi Matsuo

Satoshi Tsuchiya

Masahiro Nishimoto

Hirotaka Kashiwagi

Yoshikazu Nishimura

Takuya Shiraishi

Masahide Aoki

Satoshi Tanida

Nobuyuki Hori

Shoshin Yoshida

Takuma Kamon

Hiroko Ogawa

Kyoko Oguri

Takahiro Kawai

Tsutomu Sato

Hitoshi Yoshino

Yoshiyuki Furuta

Atsushi Ohta

Yusuke Yamagishi

Koji Takano

Mikimasa Tanada

Tatsuya Kato

Kaori Kimura

Takashi Emura

Tetsuo Kojima

Hitoshi Iikura

Ryuichi Takeyama

Naoaki Murao

Nozomi Hisada

Ryusuke Takano

Takuya Torizawa

Kousuke Asou

Kazuhiko Nakano

Miki Kojima

Takeo Iida

Shiori Kariyuki

Tomoyuki Igawa

Taichi Kuramochi

Hiroyuki Tsunoda

Atsuhiko Maeda

Naoka Hironiwa

Tatsuhiko Tachibana

Hirotake Shiraiwa

Shojiro Kadono

Futa Mimoto

Satoru Ikegami

Hajime Miyamoto

Toshiya Ito

Tatsuhiro Harada

Akihiko Okuyama

Yoichiro Hoshina

Minoru Tamiya

Aya Chiyoda

An object of the present invention is to provide methods of discovering drugs effective for tough targets, which have conventionally been discovered only with difficulty. The present invention relates to novel methods for cyclizing peptide compounds, and novel peptide compounds and libraries comprising the same, to achieve the above object.

Peptide-compound cyclization method

The present invention provides a compound having the basic structure shown by Formula (I) in which the indole ring and the pyrazolopyridine structure is bound through a substituent, a salt thereof or a solvate of either the compound or a salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound, salt or solvate as an active ingredient.

Pyrazolopyridine derivative having GLP-1 receptor agonist effect

The present inventors found cyclic peptide compounds that interact with Ras, and non-natural amino acids useful for the production of the cyclic peptide compounds. The inventors also found that the cyclic peptide compounds inhibit the binding between Ras and SOS. In addition, the inventors found specific non-natural amino acids contained in the cyclic peptide compounds and methods for production thereof.

Cyclic peptide compound having Kras inhibitory action

The present invention provides modified aminoacyl-tRNA synthetases (ARSs) having increased reactivity with N-methyl amino acids compared to natural aminoacyl-tRNA synthetases. The modified aminoacyl-tRNA synthetases according to the present invention can aminoacylate tRNAs with their corresponding N-methyl-substituted amino acids such as N-methyl-phenylalanine, N-methyl-valine, N-methyl-serine, N-methyl-threonine, N-methyl-tryptophan and N-methyl-leucine more efficiently than natural aminoacyl-tRNA synthetases. The present invention enables a more efficient production of polypeptides containing N-methyl amino acids.

Modified aminoacyl-tRNA synthetase and use thereof

The present invention provides the compound, 3-[(1S,2S)-1-[5-[(4S)-2,2-Dimethyloxan-4-yl]-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-4-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one, or a pharmaceutically acceptable salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound.

The present inventors have successfully prepared an antibody Fc region dimer that has binding activity against each of an antigen and Fc&#x3b3;R, but does not bind to the antigen and the Fc&#x3b3;R at the same time, and a polypeptide comprising the Fc region dimer. The present invention enables the preparation of a multispecific binding polypeptide capable of avoiding an adverse reaction that may be caused by its binding to an antigen and Fc&#x3b3;R at the same time. Thus, the present invention provides a polypeptide suitable as a drug.

Antigen-binding molecule containing modified Fc region

The present invention provides modified aminoacyl-tRNA synthetases (ARSs) having increased reactivity with N-methyl amino acids compared to natural aminoacyl-tRNA synthetases. The modified aminoacyl-tRNA synthetases according to the present invention can aminoacylate tRNAs with their corresponding N-methyl-substituted amino acids such as N-methyl-phenylalanine, N-methyl-valine, N-methyl-serine, N-methyl-threonine, N-methyl-tryptophan, and N-methyl-leucine more efficiently than natural aminoacyl-tRNA synthetases. The present invention enables a more efficient production of polypeptides containing N-methyl amino acids.

An objective of the present invention is to decrease the immunogenicity of mouse-derived anti-AXL antibodies in humans by humanizing them. The present invention provides antibodies that can bind to a specific region in Anexelekto (AXL) and humanized antibodies that are produced based on such antibodies. The anti-AXL antibodies of the present invention have high antitumor activity, and are useful as agents for decreasing the AXL expression level, antitumor agents, and diagnostic agents for cancer.

Anti-AXL antibody

Growing community of inventors

Shizuoka, Japan

Atsushi Matsuo