CAS 75567-37-2: Ingenol mebutate

Applications Ingenol 3-Angelate is known to exhibit antitumor activities which induces plasma membrane and mitochondrial disruption and necrotic cell death. References Ogbourne, S.M., et al.: Cancer. Res., 64, 2833 (2004); Zayed, S.M., et al.: J. Cancer. Res. Clin. Oncol., 127, 40 (2001);

Ingenol mebutate activates PKC-α, -β, -γ, -δ, -ε (Kis 0.105-0.376 nM), has anti-inflammatory and antitumor effects.

Ingenol mebutate

Ingenol-3-angelate shows anticancer activity, and P-gp-mediated absorptive transport, dermal penetration, and vascular damage contribute to the anticancer activity of ingenol-3-angelate in vivo; it activates a broad range of PKC isoforms and induces apoptosis in acute myeloid leukemia cells by activating the PKC isoform PKCdelta. Ingenol-3-angelate suppresses HIV infection of primary CD4+ T cells through down-modulation of cell surface expression of HIV co-receptors. Ingenol-3-angelate emerges as a unique local chemotherapeutic immunostimulatory debulking agent that could be used in conjunction with immunotherapies to promote regression of metastases.

Ingenol-3-angelate (ING) is a natural compound that induces apoptosis in cancer cells by inhibiting mitochondrial membrane potential and the production of ATP. It also has been shown to be an active antiretroviral therapy that inhibits HIV replication in T cells. Ingenol-3-angelate has significant cytotoxicity against k562 cells, which can be enhanced by laser ablation. The drug is metabolized to mebutate, which is the only known active form of ING. Mebutate binds to the polymerase chain reaction enzyme DNA polymerase and prevents its activity, thus inhibiting DNA synthesis and replication. Ingenol-3-angelate also has drug interactions with other drugs such as cyclosporin A and tacrolimus, which inhibit or induce cytochrome P450 enzymes.