Covalent chemistry for the RAS mutations that still have no drug
One RAS mutation can now be drugged because it offers a reactive handle. Most RAS mutations do not, so new chemistry is needed to grab other amino acids.
KRAS G12C inhibitors work by covalently modifying a cysteine. G12D, G12V and G13D, which together account for most RAS-driven cancer, lack that cysteine. Aspartate-targeting and lysine-targeting covalent chemistries, non-covalent tri-complex RAS(ON) inhibitors and pan-RAS agents are all in early clinical development. The proposal is a focused public-private chemistry programme on non-cysteine covalent warheads with tolerable reactivity, plus open sharing of failed warhead chemotypes.
- The undruggable drivers · The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.
Pages like this
not linked directly; found by shared links- RoadmapKRAS roadmap: undruggable → G12C → pan-RAS
Shares Revolution Medicines, Adagrasib, Daraxonrasib, Sotorasib.
- ProductElironrasib
Shares Revolution Medicines, KRAS & RAS inhibitors, KRAS, The undruggable drivers.
- ProductZoldonrasib
Shares Revolution Medicines, Daraxonrasib, KRAS & RAS inhibitors, KRAS.
- Key paperOstrem and Shokat: the hidden pocket that made KRAS G12C druggable
Shares Adagrasib, Daraxonrasib, Sotorasib, KRAS & RAS inhibitors.
- PersonKevan M. Shokat
Shares Adagrasib, Sotorasib, KRAS & RAS inhibitors, KRAS.
- IdeaOff-the-shelf KRAS vaccines after pancreatic cancer surgery
Shares Daraxonrasib, KRAS & RAS inhibitors, KRAS, The undruggable drivers.
- TrialRASolute 302
Shares Daraxonrasib, KRAS & RAS inhibitors, KRAS, The undruggable drivers.
- TermKRAS mutation subtypes (G12C, G12D, G12V)
Shares Adagrasib, Sotorasib, KRAS & RAS inhibitors, KRAS.