GNE-618

• CAT Number: I017868
• CAS Number: 1362151-42-5
• Molecular Formula: C21H15F3N4O3S
• Molecular Weight: 460.43
• Purity: ≥95%
• Synonyms: N-[[4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide
• InChI: InChI=1S/C21H15F3N4O3S/c22-21(23,24)16-2-1-3-18(9-16)32(30,31)17-6-4-13(5-7-17)10-26-20(29)15-8-14-12-27-28-19(14)25-11-15/h1-9,11-12H,10H2,(H,26,29)(H,25,27,28)
• InChIKey: LKBHAGGICJWHQQ-UHFFFAOYSA-N
• SMILES: C1=CC(=CC(=C1)S(=O)(=O)C2=CC=C(C=C2)CNC(=O)C3=CN=C4C(=C3)C=NN4)C(F)(F)F

GNE-618 is a potent, orally active nicotinamide phosphoribosyl transferase (NAMPT) inhibitor with an IC50 of 6 nM. GNE-618 depletes NAD levels and induces tumor cell death. Anti-tumor activity[1].
GNE-618 reduces levels of NAD with an EC50 of 2.6 nM in the NSCLC cell line Calu-6[1].
GNE-618 (10-30 nM; 72 hours) reveals an increase in the sub-2N population and a decreases in the percentage of cells in the G1 and M phases of the cell cycle in Calu-6 cells[1].
GNE-618 also reduces cellular proliferation of Calu-6 cells as determined using two different assay formats, either measuring ATP (EC50 of 13.6 ± 1.8 nM) or total protein content (SRB assay; EC50 of 25.8 ± 4.2 nM)[1]
GNE-618 (100 mg/kg; p.o.; twice daily for 5 days) significantly inhibits tumor growth by 88% and has minimal effects on body weight in STO#81 patient-derived gastric model[1].

Reference

[1]. Xiao Y, et al. Dependence of tumor cell lines and patient-derived tumors on the NAD salvage pathway rendersthem sensitive to NAMPT inhibition with GNE-618. Neoplasia. 2013 Oct;15(10):1151-60.
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