Cyclic Peptide Ligands of the Oncoprotein KRAS (G12D)

The RAS family of genes is frequently mutated in cancer and drive tumor formation and is associated with poor outcomes. Within this family, KRAS mutations account for 83% and occur in ~11% of all cancers. Several KRAS mutation variants exist with KRAS …

The RAS family of genes is frequently mutated in cancer and drives tumor formation and is associated with poor outcomes. Within this family, KRAS mutations account for 83% and occur in ~11% of all cancers. Several KRAS mutation variants exist with KRAS (G12D) being the most common, representing ~33.4%. Currently, there are no FDA-approved therapies targeting this variant. In fact, only one therapy has been approved for KRAS: sotorasib for the subtype KRAS (G12C) in 2021. KRAS (G12C) accounts for ~11.3% of KRAS mutations. As the global cancer burden is expected to grow annually, with 27.5 million new annual cases forecasted in 2040, novel therapies targeting KRAS (G12D) are urgently needed.

Towards the development of novel treatments, UCSF scientists have recently identified cyclic peptide ligands to preferentially inhibit the activity of KRAS (G12D). These chemical inhibitors bind to KRAS (G12D) by taking advantage of state-selective conformational changes and effectively diminish oncogenic functioning. 

Website:

https://techtransfer.universityofcalifornia.edu/NCD/32765.html?utm_source=AUTMGTP&utm_medium=webpage&utm_term=ncdid_32765&utm_campaign=TechWebsites

Advantages:

  • Selectively targets KRAS (G12D) mutation and not wildtype KRAS
  • Expands treatment strategies for several cancers 

Contact Information:

Name: Catherine Smith

Email: Catherine.Smith2@ucsf.edu

Phone: 510-646-0631