Description
NG 52 is a tri-substituted purine that binds to the ATP-binding site of yeast cyclin-dependent kinases, inhibiting Cdc28p and Pho85p (IC
50s = 7 and 2 μM, respectively). It is ineffective against the yeast kinases Kin28p, Srb10, and Cak1p. NG 52 is cell permeable and inhibits the growth of
S. cerevisiae (GI
50 = 30 μM). It is an analog of purvalanol A , a potent inhibitor of mammalian cyclin-dependent kinases.
Uses
NG 52 is a potent, cell-permeable, selective, ATP-compatible and orally active Cdc28p and Pho85p kinase inhibitor with IC50s of 7 μM and 2 μM, respectively. NG 52 also inhibits the activity of phosphoglycerate kinase 1 (PGK1) with an IC50 of 2.5 μM. NG 52 is inactive against yeast kinases Kin28p, Srb10, and Cak1p[1][2].
in vivo
NG 52 (50-150 mg/kg; oral administration; daily; for 13 days) treatment dose-dependently suppresses the growth of glioma xenograft[2].
| Animal Model: | Female nu/nu mice (5-week-old) injected with glioma cells[2] |
| Dosage: | 50 mg/kg, 100 mg/kg, 150 mg/kg |
| Administration: | Oral administration; daily; for 13 days |
| Result: | Dose-dependently suppressed the growth of glioma xenograft.
|
IC 50
cdc2-cyclin B: 0.34 μM (IC
50); Pho85p: 2 nM (IC
50); Cdc28p: 7 μM (IC
50); Phosphoglycerate kinase 1 (PGK1): 2.5 μM (IC
50)
References
[1] ray NS, Wodicka L, Thunnissen AM et al. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science. 1998 Jul 24;281(5376):533-8. DOI:
10.1126/science.281.5376.533[2] Wen-Liang Wang, et al. Pharmacologically inhibiting phosphoglycerate kinase 1 for glioma with NG52. Acta Pharmacol Sin. 2020 Jul 31. DOI:
10.1038/s41401-020-0465-8
