Natural product-based anti-cancer agents: aza-Englerin analogues

Chemotherapy resistance in a wide array of cancers is often associated with enhanced glucose uptake and dysregulation of the insulin signaling pathway.  Therapeutics capable of inhibiting insulin signaling would be valuable as a stand-alone treatment and for sensitizing resistant tumors to standard chemotherapy regiments.  Researchers at NCI’s Genitourinary Malignancies Branch have synthesized and developed a series of Englerin-A analogues with potent anti-tumor activity that is linked to inhibition of the insulin pathway.

The researchers have previously shown that Englerin A has potent activity in vivo using a renal carcinoma xenograft mouse model.  A new lead compound with specific activity against renal cell carcinoma, which can be synthesized to scale for in vivo studies, and improved oral bioavailability, has been identified. The NCI seeks partners interested in collaborative research to co-develop this therapeutic with an initial goal of preclinical evaluation leading to clinical testing.

Competitive Advantages:

• Novel compounds with potent and selective inhibitory effect on select cancer cells 
• Parent compounds are effective in in vivo cancer models.
• Demonstrated bioavailability after oral administration (mouse model)

Commercial Applications:

• Chemotherapeutic for renal cell carcinoma, in addition to glucose dependent tumors. 
• Treatment of diseases or conditions associated with insulin resistance