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.

Potential Commercial Applications: Competitive Advantages:
  • Chemotherapeutic for renal cell carcinoma, in addition to glucose dependent tumors. 
  • Treatment of diseases or conditions associated with insulin resistance
  • 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)

Development Stage:
Pre-clinical (in vivo)

Related Invention(s):


John Beutler (NCI)  ➽ more inventions...

Douglas Figg (NCI)  ➽ more inventions...

William Chain

Intellectual Property:
Application No. 61/936,285
Application No. 62/018,381

Ratnayake R, et al. PMID 19061394
Li Z, et al. PMID 21476574
Akee R, et al. PMID 22280462
Sourbier C, et al. PMID 23352416

Collaboration Opportunity:

Licensing and research collaboration

Licensing Contact:
John Hewes, Ph.D.
Phone: 240-276-5515

OTT Reference No: E-090-2014
Updated: Dec 20, 2017