Novel Fendiline Derivatives for the Treatment of KRAS Mutant Tumors

Dr. John F. Hancock and colleagues identified novel Fendiline derivatives for the treatment and prevention of KRAS-driven cancers.

Background:

The Ras protein family members belong to a class of proteins called small GTPases and when activated by incoming signals, it subsequently switches on other genes involved in cell growth, differentiation, and survival. As a result, mutations in the ras genes can lead to production of permanently activated Ras proteins and ultimately lead to cancer. Localization of K-ras to the plasma membrane is required for the activation of downstream effector pathways. Fendiline hydrochloride has been identified as a specific inhibitor of plasma membrane localization of K-Ras. Therefore, Fendiline and Fendiline derivatives may potentially have utility as K-Ras-specific anticancer therapeutics.

Market:

Mutations that permanently activate Ras are found in 20-25% of all human tumors and up to 90% in certain types of cancer, such as pancreatic cancer. The broad indications place a tremendous demand and market for novel compounds and methods to treat and prevent cancer by inhibition of the Ras pathway.

Technology Highlights:

• Describes novel compounds, including Fendiline derivatives, inhibiting K-Ras localization onto the plasma membrane.
• Such novel compounds may be used for inhibiting the signal transduction from oncogenic K-Ras.
• Provides potential therapies for cancer, such as leukemia, colorectal cancer, pancreatic cancer, and lung cancer.
• Available pre-clinical data in K-Ras transformed pancreatic, endometrial, colorectal and lung tumor cell lines.

IP Status:

• Issued US Patent No. 12,043,602
• Issued US Patent No. 9474730

Available for licensing

Researchers:

Drs. John F. Hancock (UTHealth) and Dharini van der Hoeven