Structural development of biological response modifiers based on thalidomide.
Thalidomide (N-alpha-phthalimidoglutarimide) is a teratogenic hypnotic/sedative agent which was used widely in the late 1950s and the early 1960s. In spite of its withdrawal from the market because of its severe teratogenicity, there has been a resurgence of interest in the drug in recent years due to its potential usefulness for the treatment of various diseases, including acquired immunodeficiency syndrome (AIDS) and various cancers. It has been revealed that thalidomide elicits pleiotropic effects and is a multi-target drug. Our structural development studies of thalidomide, focusing on tumor necrosis factor-alpha(TNF-alpha) production-regulating activity, anti-androgenic activity, puromycin-sensitive aminopeptidase-inhibiting activity, alpha-glucosidase-inhibiting activity, and inhibitory activities toward some other enzymes, are reviewed in relation to the pharmacological effects of thalidomide.
Hashimoto
Yuichi
Y
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. hashimot@iam.u-tokyo.ac.jp
D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000726:Androgen Antagonists; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D065089:Glycoside Hydrolase Inhibitors; D007155:Immunologic Factors; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide