Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma.
We have explored the mechanism of the antiangiogenic effects of thalidomide by structure-activity studies. These investigations revealed that angiogenesis inhibition correlates with teratogenicity but not with tumor necrosis factor-alpha (TFA-alpha) inhibition. Additionally, one analog of thalidomide, 3-aminothalidomide, exhibited an unusual capacity to directly inhibit myeloma cell proliferation. This activity did not correlate with TNF-alpha inhibition. Thus 3-aminothalidomide was found to inhibit multiple myeloma through effects on both the tumor and vascular compartment. The effects of an inhibitor of both the tumor and vascular compartments of a tumor on tumor growth may be synergistic.
D'Amato
R J
RJ
Enders 1006, Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA.
Lentzsch
S
S
Anderson
K C
KC
Rogers
M S
MS
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000187:drug effects; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D016207:Cytokines; D013792:Thalidomide