Kyushu University

Japan Science and Technology Agency

Yoshinori Fukui

Takehito Uruno

Takehiko Sasazuki

Yuki Sugiura

Shigeyuki Yokoyama

Motomu Kanai

Shigeki Matsunaga

Takahiro Shirai

Teruki Honma

Daisuke Takaya

Kazuhiko Yamamura

Masutaka Furue

Mutsuko Niino

An immunoregulatory agent containing a regulatory agent that regulates Dedicator of cytokinesis 2 (DOCK2)-mediated Rac activation as an active ingredient is provided.

Immunoregulatory agent

The present invention provides a compound capable of being used as an active ingredient of an anti-cancer agent. To provide an anti-cancer agent with few side effects, an object of the present invention is to provide a compound capable of selectively inhibiting the target, i.e., DOCK1, or a salt thereof. The pyridinone compound of the present invention is represented by Formula (1):  

Pyridinone compound and use thereof

An atopic dermatitis model non-human animal, containing a gene mutation in which a complex containing dedicator of cytokinesis 8 (DOCK8) protein, mammalian STE20-like kinase 1 (MST1) protein, and endothelial PAS domain protein 1 (EPAS1) protein is not formed in CD4T cells.

Atopic dermatitis model non-human animal and use thereof

The present invention provides a animal model useful in identifying a molecule controlling in a lymphocyte-specific manner migration and thus elucidating immune-related diseases and pathogenic conditions such as allergy, autoimmune diseases, GvH and graft rejections at a molecular level, or in developing a novel therapy. A nonhuman animal model such as a DOCK2 knockout mouse, in which the function to control lymphocyte migration has been deleted or suppressed, is generated by deleting DOCK2 gene on the chromosome. In this DOCK2 knockout mouse, the function of activating Rac to mediate actin cyteskeleton, the lymphocyte migration function in response to stimuli with chemokines such as SLC, SDF-1, BLC, the homing function to secondary lymphoid organs such as spleen, lymph nodes and Peyer's patches, and the function of emigrating mature thymic T cells into peripheral blood in response to stimulus with chemokine ELC are impaired, and as a result of this, immune responses are suppressed.

Nonhuman model animal lacking the ability to control lymphocyte migration

The present invention is related to provide a method for screening a substance interfering in the association of DOCK2 and ELMO1, a method for screening a substance interfering in the association of ELMO1 and Tiam1, and a method for searching a therapeutic agent for immune related diseases such as allergy, autoimmune diseases, GvH, graft rejection with the use of these searching methods, and so on. It was found that in DOCK2-mutant lacking 504 amino acid residues at the N terminus of DOCK2, Rac-activating ability was significantly decreased, and that actin polymerization could not be induced, and ELMO1 was identified as a molecule binding to this domain. It was found that DOCK2 was associated to ELMO1 via SH3 domain. Moreover, it was found that ELMO1 is bound with Tiam1 functioning as Rac-specific GDP/GTP exchange factor (GEF). It was found that DOCK2 activates Rac by recruiting Tiam1 via ELMO1.

Method of screening a substance interfering in the association of DOCK2 and ELMO

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Fukuoka, Japan

Yoshinori Fukui