A FIRST-IN-CLASS RALGDS INHIBITOR AS AN ANTI-RAS DRUG (15017)
- Detailed Technology Description
- None
- *Abstract
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A FIRST-IN-CLASS RALGDS INHIBITOR AS AN ANTI-RAS DRUG (15017)
This technology has been awarded an ExCITEcompetitive grant specifically for commercialization. The grant review committee includesrepresentatives from the pharmaceutical industry, NIH, FDA, CMS, and USPTO.
Features and Benefits Summary
Identification of novel pan-RalGEF inhibitors for treatment of Ras-driven cancers
Successfully inhibits Ras-driven tumor cells in vitro and in vivo as demonstrated in mouse studies
Provides targeted therapy with low toxicity
*This Technology is available for licensing, further development, or industrial partnering*
Market Opportunities
30% of all human cancers are driven by mutations in Ras genes. Defects in regulators of Ras are also common (for example, mutations in NF1 tumor suppressor, a negative regulator of Ras, are found in 11% of lung cancers), making it likely that the majority of human tumors are driven by aberrant Ras function. Ras has been an obvious candidate for targeted cancer therapy for almost 25 years, but attempts to inhibit Ras directly have been unsuccessful. Recent efforts have targeted PI-3 Kinase and RAF, two of the three major classes of Ras effector proteins. This line of work has resulted in many clinical candidates, but none that are particularly effective cancer therapeutics. Due largely to technical reasons, the search for inhibitors of the third major class of Ras effectors, RalGDS, has been neglected, and there are currently no inhibitors of RalGDS on the market.
Technology
The RalGDS pathway is essentialfor Ras-driven cancer and metastasis invivo in humans, as Rals modulate multiple biological pathways that arevital for tumorigenesis and metastasis. Researchers at the University ofLouisville have developed C4, a first-in-class RalGDS inhibitor. C4 is a pan-RalGEF inhibitor with nM activityand high specificity and low toxicity. In vivo studies have demonstratedthat C4 supresses metastasis of Ras-driven cancer cell lines. Several compounds derived from an initialround of medicinal chemistry retain activity.
Upper Panels:Panc-1 and MiaPaCa-2 mutant Ras containing pancreatic tumor cell lines wereplated in the presence of 10 µM or 0.9 µM of drug. Lower Panel: Compound tested for toxicity.
Technology Status
- IP Status: PCT Application Filed
- Development Status: Testingof first gen derivative comps complete; preliminary animal studies.
- Fields of Use Available: All
Researchers:
- Dr. Geoffrey Clark
- Dr. John Trent
- Dr. Joseph Burlison
- Country/Region
- USA
