T
Takumi Ito
Researcher at Tokyo Medical University
Publications - 44
Citations - 4182
Takumi Ito is an academic researcher from Tokyo Medical University. The author has contributed to research in topics: Cereblon & Thalidomide. The author has an hindex of 15, co-authored 40 publications receiving 3280 citations. Previous affiliations of Takumi Ito include National Presto Industries & Celgene.
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Journal ArticleDOI
Identification of a Primary Target of Thalidomide Teratogenicity
Takumi Ito,Hideki Ando,Takayuki Suzuki,Toshihiko Ogura,Kentaro Hotta,Yoshimasa Imamura,Yuki Yamaguchi,Hiroshi Handa +7 more
TL;DR: A basis for thalidomide teratogenicity is revealed and may contribute to the development of new thalidmide derivatives without teratogenic activity.
Journal ArticleDOI
Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.
Antonia Lopez-Girona,Derek Mendy,Takumi Ito,Karen Miller,Anita Gandhi,Jian Kang,Satoki Karasawa,Gilles Carmel,Pilgrim Jackson,Mahan Abbasian,Afshin Mahmoudi,Brian E. Cathers,Emily Rychak,Svetlana Gaidarova,Roger Shen-Chu Chen,Peter H. Schafer,Hiroshi Handa,Thomas O. Daniel,Jilly F. Evans,Rajesh Chopra +19 more
TL;DR: Biophysical, biochemical and gene silencing studies show that CRBN is a proximate, therapeutically important molecular target of lenalidomid and pomalidomide.
Journal ArticleDOI
Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.).
Anita Gandhi,Jian Kang,Courtney G. Havens,Thomas Conklin,Yuhong Ning,Lei Wu,Takumi Ito,Hideki Ando,Michelle Waldman,Anjan Thakurta,Anke Klippel,Hiroshi Handa,Thomas O. Daniel,Peter H. Schafer,Rajesh Chopra +14 more
TL;DR: This work presents a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4CRBN, leading to their ubiquitination, subsequent proteasomal degradation and T cell activation.
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Structure of the human Cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs
Philip P Chamberlain,Antonia Lopez-Girona,Karen Miller,Gilles Carmel,Barbra Pagarigan,Barbara Chie-Leon,Emily Rychak,Laura G. Corral,Yan J Ren,Maria Wang,Mariko Riley,Silvia L. Delker,Takumi Ito,Hideki Ando,Tomoyuki Mori,Yoshinori Hirano,Hiroshi Handa,Toshio Hakoshima,Thomas O. Daniel,Brian E. Cathers +19 more
TL;DR: The crystal structure of human CRBN bound to DDB1 and the drug lenalidomide is presented and it is shown that a hydrophobic pocket in the thalidomid-binding domain (TBD) of CRBN accommodates the glutarimide moiety of lenalidmide, whereas the isoindolinone ring is exposed to solvent.
Journal ArticleDOI
A novel cereblon modulator recruits GSPT1 to the CRL4 CRBN ubiquitin ligase
Mary E Matyskiela,Gang Lu,Takumi Ito,Barbra Pagarigan,Chin-Chun Lu,Karen Miller,Wei Fang,Nai-Yu Wang,Derek Nguyen,Jack Houston,Gilles Carmel,Tam Tran,Mariko Riley,Lyn'Al Nosaka,Gabriel C. Lander,Svetlana Gaidarova,Shuichan Xu,Alexander L. Ruchelman,Hiroshi Handa,James Carmichael,Thomas O. Daniel,Brian E. Cathers,Antonia Lopez-Girona,Philip P Chamberlain +23 more
TL;DR: Findings define a structural degron underlying cereblon ‘neosubstrate’ selectivity, and identify an anti-tumour target rendered druggable by Cereblon modulation.