In vitro activity: DKM 2-93 is a covalent and selective inhibitor of the ubiquitin-like modifier activating enzyme 5 (UBA5). DKM 2-93 is a covalent ligand that impairs pancreatic cancer cell survival and in vivo tumor growth through covalently modifying the catalytic cysteine of UBA5, thereby inhibiting its activity as a protein that activates the ubiquitin-like protein UFM1 to UFMylate proteins. UBA5 is a novel pancreatic cancer therapeutic target and DKM 2-93 as a relatively selective lead inhibitor of UBA5.

Kinase Assay: DKM 2-93 impairs pancreatic cancer cell survival through covalently modifying the catalytic cysteine of UBA5, thereby inhibiting its activity as a protein that activates the ubiquitin-like protein UFM1 to UFMylate proteins. DKM 2-93 inhibits PaCa2 and Panc1 cells survival with IC50s of 90 and 30 μM, respectively. Ubiquitin-like modifier activating enzyme 5 (UBA5) is a novel pancreatic cancer therapeutic target.

Cell Assay: DKM 2-93 inhibits PaCa2 and Panc1 cells survival with IC50s of 90 and 30 μM, respectively. Ubiquitin-like modifier activating enzyme 5 (UBA5) is a novel pancreatic cancer therapeutic target.