Discovery of Allosteric Non-Covalent KRAS Inhibitors



RAS mutations account for >15% of all human tumors, and of these ~85% are due to mutations in a particular RAS gene: KRAS. Currently, there are no approved drugs that can directly act on mutated KRAS to stop its cancer causing activities.

Dr. Gorfe at UTHealth has used a structure based computational ligand design approach followed by biophysical and cell biological experiments to discover a number of non-covalent allosteric inhibitors that target some of the most common mutant forms of KRAS including, G12V, G12D, G13D, Q61H as well as G12C.



One of these ligands, named Compound 11, is a first-in-class pyrazolopyrimidine-based KRAS inhibitor with exceptionally good inhibitory profile. This compound:

- binds to GTP-KRAS with high affinity

- disrupts effector Raf binding

- reduces signal transduction through KRAS, and

- inhibits proliferation of cancer cells harboring mutant KRAS.

In addition, while compound 11 binds to active GTP-bound KRAS with a Kd of 200-1000 nM, it does not bind to inactive GDP-KRAS or to GDP- or GTP-bound NRAS and HRAS, two close homologs of KRAS.




Intellectual Property Status:

- Patent Pending

- Available for licensing

Patent Information:

The preceding is intended to be a non-confidential and limited description of a novel technology created at the University of Texas Health Science Center at Houston (UTHealth). This promotional material is not comprehensive in scope and should not replace company’s diligence in a thorough evaluation of the technology. Please contact the Office of Technology Management for more information regarding this technology.
For Information, Contact:
Hannah Nelson
Senior Technology License Associate
University of Texas Health Science Center At Houston
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