Identification of a Primary Target of Thalidomide Teratogenicity

American Association for the Advancement of Science (AAAS) - Tập 327 Số 5971 - Trang 1345-1350 - 2010
Takumi Ito1, Hideki Ando2, Takayuki Suzuki3,4, Toshihiko Ogura3, Kentaro Hotta2, Yoshimasa Imamura5, Yuki Yamaguchi2, Hiroshi Handa2,1
1Integrated Research Institute, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
2Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan
3Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan
4Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency (JST), Saitama 332-0012, Japan.
5Drug Discovery Research, Astellas Pharma Inc., Ibaraki 305-8585, Japan.

Tóm tắt

Thalidomide Teratogenicity Target In the late 1950s and early 1960s, thalidomide was prescribed to pregnant women as a cure for morning sickness, but it was then found to have developmental defects, most obviously, stunted limbs in thousands of babies. Although its use was banned worldwide, thalidomide has since been found to be a valuable treatment for a range of cancers, inflammatory disorders, and leprosy. Several hypotheses have been proposed, but the mechanism of action of thalidomide is unknown. Using zebrafish and chicken as animal models, Ito et al. (p. 1345 ) show that the protein cereblon is a primary target of thalidomide. Thalidomide exerts teratogenic effects by binding to cereblon and inhibiting associated enzymatic activity important for limb development. Knowing the mechanism of action of thalidomide should encourage the search for thalidomide derivatives without teratogenic activity.

Từ khóa


Tài liệu tham khảo

10.1002/(SICI)1096-9926(199911)60:5<306::AID-TERA11>3.0.CO;2-Y

10.1016/j.biocel.2007.01.022

10.4161/cc.7.9.5793

10.1038/8466

10.1073/pnas.91.9.4082

10.1002/cpt196563303

10.1056/NEJM199911183412102

10.1016/S0149-2918(00)88289-2

10.1002/tcr.20170

10.1096/fj.06-7603com

10.1212/01.WNL.0000146196.01316.A2

10.1038/nature05175

10.1016/S0092-8674(03)00316-7

10.1038/nature05683

10.1016/S0092-8674(03)01074-2

10.1038/nrm1547

10.1016/j.cell.2005.02.035

10.1016/j.molcel.2006.08.010

10.1016/S0140-6736(04)16308-3

10.1038/79951

10.1203/PDR.0b013e318186e609

10.1182/blood-2004-09-3679

10.1038/416527a

10.1038/nature05838

10.1046/j.1469-7580.2001.19910099.x

10.1016/0092-8674(93)90626-2

10.1038/82601

10.1038/82609

10.1073/pnas.0901505106

10.1084/jem.177.6.1675

10.1038/sj.leu.2402295

10.1002/dvdy.10150

10.1242/dev.001677

10.1158/1078-0432.CCR-04-0421

10.1016/j.cell.2006.09.045

10.1073/pnas.0611311104

Thông tin
Thông tin xuất bản

American Association for the Advancement of Science (AAAS)

Tập 327 Số 5971

1345-1350

Thông tin tác giả