Krebsmutationen Deep Dives: KRAS und die molekulare Klebe

More on KRAS G12D in lung cancer (NSCLC): In addition to data on PROTAC (last video), there was also a recent update on the data for the G12D inhibitor zoldonrasib! The remarkable thing is that zoldonrasib is a so-called ON inhibitor, meaning it targets the active, GTP-bound form. This is where the problem lies: Only vanishingly small amounts of GTP are needed for binding between KRAS and GTP (high affinity), while there is more than enough GTP present in the cell – a fair "competition" with an inhibitor is thermodynamically impossible. BUT: Zoldonrasib is not an old-school inhibitor at all, but rather binds to CypA and KRAS G12D to form an inactive complex – molecular glue, the same principle by which other ON inhibitors work. Data from the RMC-9805-001 study were presented at the AACR congress: NSCLC patients with the KRAS G12D mutation and receiving the recommended dose. Unfortunately, the publication is not yet available – we will, of course, provide an update as soon as it is! Enjoy! Our video on the G12D degrader:    • Krebsmutationen Deep Dives: KRAS G12D star...   Our video on KRAS as a cancer mutation:    • Krebsmutationen: KRAS - The Ancient Enemy.   One of our DeepDive videos on KRAS:    • Krebsmutationen Deep Dives: KRAS-Untergrup...   00:00 Cancer Mutations Deep Dives: KRAS and Molecular Glue 01:30 Welcome [SKIP INTRO] 01:57 Zoldon Rasib... 02:34 ...and CypA (Cytophilin A) 03:32 Molecular Glue 03:54 AACR 2026 04:24 RMC-9805-001 (NSCLC Cohort) 07:58 Outlook and OUTRO ______________________________ Music: "Life is Parallel to Poetry" by baegel [Epidemic Sound]