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1. (WO2006126505) STAT FUNCTION INHIBITOR AND APPLICATION THEREOF
Latest bibliographic data on file with the International Bureau   

Pub. No.:    WO/2006/126505    International Application No.:    PCT/JP2006/310187
Publication Date: 30.11.2006 International Filing Date: 23.05.2006
IPC:
A61K 45/00 (2006.01), A61K 31/713 (2006.01), A61K 38/00 (2006.01), A61K 48/00 (2006.01), A61P 13/12 (2006.01), A61P 17/06 (2006.01), A61P 19/02 (2006.01), A61P 19/08 (2006.01), A61P 25/00 (2006.01), A61P 29/00 (2006.01), A61P 35/00 (2006.01), A61P 35/02 (2006.01), A61P 37/02 (2006.01), A61P 43/00 (2006.01)
Applicants: THE UNIVERSITY OF TOKYO [JP/JP]; 3-1, Hongo 7-chome, Bunkyo-ku, Tokyo 1138654 (JP) (For All Designated States Except US).
MIYAJIMA, Atsushi [JP/JP]; (JP) (For US Only).
KIM, Kyung-woon [KR/JP]; (JP) (For US Only).
ITOH, Tohru [JP/JP]; (JP) (For US Only)
Inventors: MIYAJIMA, Atsushi; (JP).
KIM, Kyung-woon; (JP).
ITOH, Tohru; (JP)
Agent: SHIMIZU, Hatsushi; Kantetsu Tsukuba Bldg. 6F 1-1-1, Oroshi-machi, Tsuchiura-shi Ibaraki 3000847 (JP)
Priority Data:
2005-153814 26.05.2005 JP
Title (EN) STAT FUNCTION INHIBITOR AND APPLICATION THEREOF
(FR) INHIBITEUR DE FONCTION STAT ET SON APPLICATION
(JA) STAT機能阻害剤およびその応用
Abstract: front page image
(EN)When the expression of an EZI gene is inhibited using synthetic oligo-siRNA which targets the EZI gene or siRNA which has been expressed using a vector, the nuclear translocation of STAT3 and the activation of the expression of a STAT3-dependent gene are suppressed. A nucleic acid having a modification in an APRE sequence to which EZI protein and STAT3 protein can bind in the &agr;2-macroglobulin promoter region inhibits the nuclear translocation/subcellular localization of STAT protein by EZI protein and also inhibits the activation of the expression of an STAT3-dependent gene. It is also found that a synthetic peptide having a cell membrane penetration signal bound to an STAT3-binding peptide on EZI protein inhibits the nuclear translocation/subcellular localization of STAT by EZI protein and the activation of the expression of an STAT-dependent gene and also inhibits the growth of cancer cells.
(FR)Lorsque l’expression d’un gène EZI est inhibée en utilisant un oligo-siARN synthétique qui cible le gène EZI ou siARN qui a été exprimé en utilisant un vecteur, la translocation nucléaire de STAT3 et l’activation de l’expression du gène dépendant de STAT3 sont supprimées. Un acide nucléique ayant une modification dans une séquence APRE à laquelle la protéine EZI et la protéine STAT3 peuvent se lier dans la région du promoteur de la macroglobuline &agr;2 inhibe la translocation nucléaire/la localisation sous cellulaire de la protéine STAT au moyen de la protéine EZI et inhibe aussi l’activation de l’expression d’un gène dépendant de STAT3. On a aussi découvert qu’un peptide synthétique ayant un signal de pénétration de membrane cellulaire lié à un peptide de liaison STAT3 sur la protéine EZI inhibe la translocation nucléaire/la localisation sous cellulaire de STAT au moyen de la protéine EZI et l’activation de l’expression d’un gène dépendant de STAT et inhibe aussi la croissance des cellules cancéreuses.
(JA) EZI遺伝子を標的とする合成オリゴsiRNAまたはベクターより発現させたsiRNAを用いて、EZI遺伝子の発現を抑制した結果、STAT3の核移行およびSTAT3依存性遺伝子発現活性化が抑制された。α2-マクログロブリンプロモーター領域中のEZIタンパク質およびSTAT3タンパク質が結合するAPRE配列を改変した核酸が、EZIタンパク質によるSTATタンパク質の核移動/核局在化を阻害し、さらにはSTAT依存的な遺伝子発現活性化をも抑制した。また、EZIタンパク質上のSTAT3結合ペプチドに細胞膜浸透シグナルを結合させた合成ペプチドはEZIタンパク質によるSTATの核移動/核局在化、STAT依存的な遺伝子発現活性化を抑制し、さらには、がん細胞増殖を抑制することを見出した。
Designated States: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, LY, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW.
African Regional Intellectual Property Organization (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, LT, LU, LV, MC, NL, PL, PT, RO, SE, SI, SK, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
Publication Language: Japanese (JA)
Filing Language: Japanese (JA)