The first total synthesis of the E1 ubiquitin-activating enzyme inhibitor, himeic acid A, is
reported. A McCombie reaction was used to form the core γ-pyrone via a 6π …

Targeting the activating enzymes (E1) of ubiquitin (Ub) and ubiquitin-like modifiers (Ubls)
has emerged as a promising anti-cancer strategy, possibly overcoming the ineffectiveness of …

Semisynthetic, mechanism-based protein inhibitors of ubiquitin (Ub) and ubiquitin-like
modifier (Ubl) activating enzymes (E1s) have been developed to target E1-catalyzed …

Transfer of ubiquitin to substrate proteins regulates most processes in eukaryotic cells. E2
enzymes are a central component of the ubiquitin machinery, and generally determine the …

Ubiquitin-conjugating E2 enzymes are central to the ubiquitination cascade and have been
implicated in cancer and other diseases. Despite strong interest in developing specific E2 …

Ubiquitin-activating enzyme (UAE or E1) activates ubiquitin via an adenylate intermediate
and catalyzes its transfer to a ubiquitin-conjugating enzyme (E2). MLN4924 is an adenosine …

Protein degradation via the ubiquitin-proteasome pathway is important for a diverse number
of cellular processes ranging from cell signaling to development. Disruption of the ubiquitin …

In 2002, the first natural product inhibitor of ubiquitin activating enzyme, panepophenanthrin
(1), was isolated from the mushroom strain Panus rudis Fr. IFO8994. 1 In 2003, we …

E3 ligases are genetically implicated in many human diseases, yet E3 enzyme mechanisms
are not fully understood, and there is a strong need for pharmacological probes of E3s. We …

Manipulating the activities of E3 ubiquitin ligases with chemical ligands holds promise for
correcting E3 malfunctions and repurposing the E3s for induced protein degradation in the …