GNE-618 is a potent and orally active inhibitor of nicotinamide phosphoribosyltransferase (IC50: 6 nM). GNE-618 depletes NAD levels and induces tumor cell death. It has anti-tumor activity.

NAMPT:6 nM

GNE-618 decreases levels of NAD (EC50: 2.6 nM in the NSCLC cell line Calu-6). GNE-618 also reduces cellular proliferation of Calu-6 cells as determined using two different assay formats, either measuring ATP (EC50: 13.6 nM) or total protein content (SRB assay; EC50: 25.8 nM). GNE-618 (10-30 nM; 72 hours) displays an increase in the sub-2N population and a reduction in the percentage of cells in the G1 and M phases of the cell cycle in Calu-6 cells.

In the STO#81 patient-derived gastric cancer model, GNE-618 administered orally at a dosage of 100 mg/kg twice daily for 5 days significantly inhibits tumor growth by 88%, while having minimal effects on body weight.