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Small Molecule for Treatment-Resistant Lung Cancer
Emory University
Small molecule
Oncology
Hit To Lead or Lead Optimization
• KRA-533 activates KRAS by preventing the cleavage of GTP into GDP, leading to the accumulation of GTP-KRAS, an active form of KRAS. Treatment of human lung cancer cells with KRA-533 resulted in increased KRAS activity and suppression of cell growth.
• Lung cancer patients with KRAS mutation(s) have a poor prognosis due in part to the development of resistance to currently available therapeutic interventions. Currently, there are no effective targeted therapies for patients with the KRAS mutation.
• Overcoming these hurdles, Emory researchers have identified a small molecule KRAS agonist that specifically binds the protein and induces cell death in mutant KRAS lung cancer cells. Lung cancer cell lines with KRAS mutation were relatively more sensitive to the small molecule than cell lines without KRAS mutation. Additionally, this molecule suppresses malignant growth without significant toxicity to normal tissues.
US20210137953A1
Small Molecule KRAS Agonist for Mutant KRAS Cancer Therapy. Molecular Cancer (2019)
