Enpp-1-IN-12 (compound 43), an orally active and potent inhibitor of ecto-nucleotide pyrophosphatase/phosphodiesterases 1 (ENPP1) with a K i of 41 nM, exhibits anti-tumor activity [1].

Enpp-1-IN-12 (5 μM) demonstrates a half-life exceeding 120 minutes and an intrinsic clearance rate below 11.55 μL/min/million cells in human hepatocytes, while manifesting a half-life of 61.88 minutes and a clearance rate of 22.4 μL/min/million cells within mouse hepatocytes [1].

Enpp-1-IN-12, at a dosage of 100 mg/kg administered orally, effectively inhibits tumor growth in a syngeneic murine model for lung cancer derived from LLC1 cells. At a lower dose of 10 mg/kg, the compound demonstrates moderate oral bioavailability (F=45.1%) with a half-life of 1.04 hours and a peak concentration (C max) of 303.10 ng/mL in healthy female BALB/c mice. When administered intravenously at 1 mg/kg, Enpp-1-IN-12 shows a half-life of 0.76 hours, a peak concentration of 308.64 ng/mL, and a clearance rate of 73.22 mL/min/kg in the same mouse model.