Covalent drugs have been used to treat diseases for more than a century, but tools that
facilitate the rational design of covalent drugs have emerged more recently. The purposeful …

Undruggable proteins are a class of proteins that are often characterized by large, complex
structures or functions that are difficult to interfere with using conventional drug design …

KRASG12C has emerged as a promising target in the treatment of solid tumors. Covalent
inhibitors targeting the mutant cysteine-12 residue have been shown to disrupt signaling by …

The RAS oncogene is both the most frequently mutated oncogene in human cancer and the
first confirmed human oncogene to be discovered in 1982. After decades of research, in …

One of the most common drivers in human cancer is the mutant KRAS protein. Not so long
ago KRAS was considered as an undruggable oncoprotein. After a long struggle, however …

Fragment‐based drug discovery (FBDD) is now established as a complementary approach
to high‐throughput screening (HTS). Contrary to HTS, where large libraries of drug‐like …

High‐throughput (HT) screening drug discovery, during which thousands or millions of
compounds are screened, remains the key methodology for identifying active chemical …

Conspectus Nearly a century after its first description, configurationally stable axial chirality
remains a rare feature in marketed drugs. In the development of the KRASG12C inhibitor …

The binding complexes formed by proteins and small molecule ligands are ubiquitous and
critical to life. Despite recent advancements in protein structure prediction, existing …

Protein–protein interactions (PPIs) have important roles in various cellular processes, but
are commonly described as 'undruggable'therapeutic targets due to their large, flat …