LASSBio-542: Novel Thalidomide Analog Distinctly Modulates IL-10 and Inhibits Angiogenesis
Daniel Serra de Carvalho,
Lidia Moreira Lima,
Eliezer Jesus de Lacerda Barreiro,
Tercia R. Alves,
Jose Augusto da Costa Nery,
Euzenir N. Sarno,
Elizabeth P. Sampaio.
LASSBio-542 is a thalidomide analog synthesized as a 2-phenoxy-phthalimide derivative with the ability to inhibit
Tumor Necrosis Factor-alpha (TNFα), behaving similarly in some instances to the original drug in vitro and in animal
models. In new experiments comparing the biological activities of both drugs, we identified LASSBio-542 as an immunomodulator
compound with extra properties dissimilar to those of thalidomide. While the extent of TNFα, IL-12p40
and IL-1β production stimulated by Lipopolysaccharide (LPS) inhibition was similar to thalidomide, Interleukin(IL)-10
production was inhibited by LASSBio-542; and Nuclear Factor kappa-B (NFκB) activation via proinflammatory stimulus
was also inhibited by both drugs. In the same vein, angiogenesis was impaired while endothelial cell migration was affected
by LASSBio-542 alone. Modulation of pro-angiogenic factors induced by TNFα in Human Umbilical Endothelial
Vein Cells (HUVEC) such as IL-8, Vascular Endothelial Growth Factor-A (VEGF-A), Cyclooxygenase-2(COX-2), and
TNFα itself was also observed by semiquantitative real-time PCR. The study of this molecule may provide new insights
into thalidomide mechanisms and new therapeutic options for diseases characterized by singular alterations in the cytokine
networks and angiogenesis impairments.
Keywords: Thalidomide, TNFα, IL-10, VEGF, angiogenesis, NFκB, immunomodulator, LASSBio-542, angiogenesis, COX.
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