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a phthalimide derivative that inhibits centrosomal clustering is effective on multiple myelomaphthalimide导数在多发性骨髓瘤抑制centrosomal聚类是有效的
A Phthalimide Derivative That Inhibits Centrosomal
Clustering Is Effective on Multiple Myeloma
1 2 1 1 1
Hirokazu Shiheido , Fukiko Terada , Noriko Tabata , Ichigo Hayakawa , Nobutaka Matsumura ,
1 1 3 3 4 4
Hideaki Takashima , Yoko Ogawa , Wenlin Du , Taketo Yamada , Mitsuru Shoji , Takeshi Sugai ,
1 2 2 1
Nobuhide Doi , Shiro Iijima , Yutaka Hattori , Hiroshi Yanagawa *
1 Department of Biosciences and Informatics, Keio University, Hiyoshi, Kohoku-ku, Yokohama, Japan, 2 Clinical Physiology and Therapeutics, Faculty of Pharmacy, Keio
University, Minato-ku, Tokyo, Japan, 3 Department of Pathology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan, 4 Organic and Biocatalytic Chemistry,
Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, Japan
Abstract
Despite the introduction of newly developed drugs such as lenalidomide and bortezomib, patients with multiple myeloma
are still difficult to treat and have a poor prognosis. In order to find novel drugs that are effective for multiple myeloma, we
tested the antitumor activity of 29 phthalimide derivatives against several multiple myeloma cell lines. Among these
derivatives, 2-(2,6-diisopropylphenyl)-5-amino-1H-isoindole-1,3- dione (TC11) was found to be a potent inhibitor of tumor
cell proliferation and an inducer of apoptosis via activation of caspase-3, 8 and 9. This compound also showed in vivo
activity against multiple myeloma cell line KMS34 tumor xenografts in ICR/SCID mice. By means of mRNA display selection
on a
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