Immunosuppressive effects of Ovalicin-semicarbazone

Cell cycle inhibition by the anti-angiogenic agent TNP-470 is mediated by p53 and p21 WAF1/CIP1

“…However, both fumagillin and TNP-470 were also reported to have similar effects on other cell types, including fibroblasts (4,9). The related natural product ovalicin was in fact initially identified as an immunosuppressive agent affecting lymphoid cells (18), and TNP-470 has also been found to be immunosuppressive (16). It is worth noting that, of various cell types examined so far, endothelial cells are among the most sensitive cell type to TNP-470 treatment.…”

Stereoselective Total Synthesis of (-)-Ovalicin

“…2 It also exhibits antibiotic, antitumor and immunosuppressive properties. 3,4 TNP-470, a semi-synthetic derivative of fumagillin, has also been shown to inhibit angiogenesis and reduce the proliferation of endothelial cells 5 (Figure 1). This wide range of activities of ovalicin has attracted several research groups to accomplish its synthesis using different chemical approaches.…”

Natural product-based PROteolysis TArgeting Chimeras (PROTACs)

“…42 It was found to be an effective angiogenesis inhibitor through suppression of endothelial cell proliferation. 43,44 The molecular target of ovalicin 1 was identified as a common bifunctional protein, type 2 methionine aminopeptidase (MetAP2), that acts as an inhibitor of eukaryotic initiation factor 2α (elF-2α) phosphorylation. 45 A 10-mer peptide within IκBα (DRHDSGLDSM), a negative regulator of NFκB, has been shown to bind the F box protein of the heterotetrameric Skp1-Cullin-F (SCF) complex and to promote the ubiquitination and degradation of IκBα.…”