Small molecule analogs of the naturally-occurring compound solenopsin for the treatment of various cancers including melanoma and angiosarcoma.
- Analogs derived from a naturally-occurring alkaloid.
- Potential treatment of cancers for which there is a poor prognosis or low survival rate.
Phosphoinositol-3 kinase (PI3K) and its downstream effector Akt, play a major regulatory role in control of apoptosis, proliferation, and angiogenesis. Many cancers show an overexpression of PI3K and Akt. For example, PI3K and Akt are amplified or overexpressed in sarcomas, ovarian cancer, multiple myeloma, and melanoma. There are a number of PI3K inhibitors currently in clinical phase trials, but none of these drugs have been approved. Potential anticancer agents that inhibit PI3K expression may play a key role in the treatment of sarcomas and melanomas.
Solenopsin is an alkaloid which contributes to the toxic effect of fire ant venom. Solenopsin inhibits angiogenesis via the PI3-K signaling pathway. PI3K and its downstream effector Akt, play a major regulatory role in control of apoptosis, proliferation, and angiogenesis. In addition, solenopsin has cytotoxic, hemolytic, necrotic, insecticidal, antibacterial, antifungal, and anti-HIV properties. Emory researchers have synthesized a series of analogs of solenopsin. The activity of the derived small molecules have been tested in angiosarcoma (SVR) and melanoma (A375) cell lines.
Series of analogs have been tested in vitro in angiosarcoma and melanoma cell lines.