Cell experiment:

PaCa2 and Panc1 cells are treated with 0-1000 μM DKM 2-93 for 48 hours. Cell viability is assessed by Hoescht stain[1].

Animal experiment:

Mice: Mice are subcutaneously injected with PaCa2 cells to initiate the tumor xenograft study and treatments of mice are initiated with vehicle or DKM 2-93 (50 mg/kg ip, once per day) three days after injection of cancer cells[1].

DKM 2-93 is a relatively selective inhibitor of UBA5 with an IC50 of 430 μM.

Ubiquitin-like modifier activating enzyme 5 (UBA5) is a novel pancreatic cancer therapeutic target. 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[1].

DKM 2-93 daily treatment significantly impairs tumor growth of PaCa2 cells in vivo in tumor xenograft studies in immune-deficient mice without causing any weight loss or overt toxicity[1].

[1]. Roberts AM, et al. Chemoproteomic Screening of Covalent Ligands Reveals UBA5 As a Novel Pancreatic Cancer Target. ACS Chem Biol. 2017 Apr 21;12(4):899-904.