Article

Discovery of allosteric non-covalent KRAS inhibitors that bind with sub-micromolar affinity and disrupt effector binding

2018-10-10

Abstract excerpt

Approximately 15% of all human tumors harbor mutant KRAS, a membrane-associated small GTPase and a notorious oncogene. Somatic mutations that render KRAS constitutively active lead to uncontrolled cell growth, survival, proliferation, and eventually cancer. KRAS is thus a critical anticancer drug target. However, despite aggressive efforts in recent years, there is no drug on the market that directly targets KRAS....

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: dcd19d51-8bda-53e8-a847-5dfc5294042d
DOI: 10.1101/440487

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Discovery of allosteric non-covalent KRAS inhibitors that bind with sub-micromolar affinity and disrupt effector bindingDOI 10.1101/440487Read

Small-Molecule Inhibitors Directly Targeting KRAS as Anticancer Therapeutics.Semantic proximity Read

Biophysical and Biochemical Characterization of Structurally Diverse Small Molecule Hits for KRAS Inhibition.Semantic proximity Read

The energetic and allosteric landscape for KRAS inhibitionSemantic proximity Read

Structural insights into small-molecule KRAS inhibitors for targeting KRAS mutant cancers.Semantic proximity Read

The energetic and allosteric landscape for KRAS inhibition.Semantic proximity Read

Analysis of KRAS-Ligand Interaction Modes and Flexibilities Reveals the Binding Characteristics.Semantic proximity Read

Pan-KRAS inhibitor disables oncogenic signalling and tumour growth.Semantic proximity Read

Crystallographic Studies of KRAS in Complex with Small Molecules and RAS-Binding Proteins.Semantic proximity Read

Structure-based inhibitor design of mutant RAS proteins-a paradigm shift.Semantic proximity Read

Expanding Addressable KRAS Mutations through the Structure- and Property-Based Design of Dual-State (GDP/GTP), Reversible Pan-KRAS Inhibitors.Semantic proximity Read

Targeting oncogenic KRasG13C with nucleotide-based covalent inhibitorsSemantic proximity Read

Design of Small Molecules That Compete with Nucleotide Binding to an Engineered Oncogenic KRAS Allele.Semantic proximity Read