Small-molecule drugs for targeted cancer therapy

This technology is a collection of small molecules for targeted cancer therapy associated with the RAS oncogene.

Unmet Need: Effective and targeted cancer therapy

Many anti-cancer drugs currently on the market come with significant side effects to patients because they are often not particularly selective for tumor cells, and can cause unwanted damage or death to normal cells. As a result, molecular targeted cancer therapeutics directed at inhibiting specific oncogenic proteins or pathways represent a promising approach to cancer drug discovery. One limitation of this approach is that some oncogenic proteins, such as the RAS oncoproteins, have been difficult to target effectively with small molecules. Therefore, there is a substantial need for identifying oncogene-selective lethal compounds that kill tumor cells only in the presence of specific oncoproteins.

The Technology: Compounds capable of specifically targeting cancer cells for improved efficacy and safety

This technology identifies RAS-selective-lethal compounds capable of inducing rapid and nonapoptotic cell death in oncogenic, RAS-containing tumorigenic cells. One such compound that displays the oncogenic-RAS-synthetic-lethality (RSL) is RSL3. The active stereoisomer of RSL3 possesses selective lethality towards tumor cells containing oncogenic RAS, without non-specific targeting of cancer cells that do not contain the specific oncogenic protein. As such, this technology provides potent drug candidates capable of targeting select cancer cells, without the risk of harming healthy cells.

These compounds exhibited selective lethality in engineered fibroblast-derived tumorigenic cell lines.

Applications:

• Targeted therapeutics for cancers associated with RAS oncoproteins
• Small-molecule drugs for cancer research related to RAS oncogenes
• Small-molecule drugs to study therapeutic efficacy with synthetic lethality
• Method of synthetic lethal screening for RAS-related cancers

Advantages:

• Better therapeutic efficiency with targeted therapy
• High-specificity
• Minimal toxicity to healthy cells

Lead Inventor:

Brent Stockwell, Ph.D.

Patent Information:

Patent Status

Related Publications:

• Skouta R, Hayano M, Shimada K, Stockwell BR. “Design and synthesis of Pictet-Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death” Bioorganic & Medicinal Chemistry Letters. 2012 Sep 1; 22(17): 5707-5713.

• Weiwer M, Bittker JA, Lewis TA, Shimada K, Yang WS, MacPherson L, Dandapani S, Palmer M, Stockwell BR, Schreiber SL, Munoz B. “Development of small-molecule probes that selectively kill cells induced to express mutant RAS” Bioorganic & Medicinal Chemistry Letters. 2012 Feb 15; 22(4): 1822-1826.

• Yang WS, Stockwell BR. “Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells” Chemistry & Biology. 2008 Mar 21; 15(3): 234-245.

Tech Ventures Reference:

• IR M10-018-a

• Licensing Contact: Joan Martinez