Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein–Protein Interaction
John M. Ketcham, Jacob R. Haling, Shilpi Khare, Vickie Bowcut, David M. Briere, Aaron C. Burns, Robin J. Gunn, Anthony Ivetac, Jon Kuehler, Svitlana Kulyk, Jade Laguer, J. David Lawson, Krystal Moya, Natalie Nguyen, Lisa Rahbæk, Barbara Saechao, Christopher R. Smith, Niranjan Sudhakar, Nicole C. Thomas, Laura Vegar, Darin Vanderpool, Xiaolun Wang, Larry Yan, Peter Olson, James G. Christensen, Matthew A. Marx
Abstract
PPI. Oral administration of MRTX0902 in combination with MRTX849 results in a significant increase in antitumor activity relative to that of either single agent, including tumor regressions in a subset of animals in the MIA PaCa-2 tumor mouse xenograft model.
Topics & Concepts
ChemistryBioavailabilityPenetrant (biochemical)PharmacologyBiochemistryOrganic chemistryMedicineProtein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingPI3K/AKT/mTOR signaling in cancer