NSC 12 is an extracellular trap of fibroblast growth factor 2 (FGF2) that binds FGF2 and interferes with its interaction with FGFR1. NSC12 inhibits the proliferation of different FGF-dependent tumour cells both in vitro and in vivo with no systemic toxic effects[1].
NSC12 (NSC 172285) is an orally available inhibitor of FGF2/FGFR interaction with potential antitumor activity.
NSC-12 can inhibit FGF-dependent tumor growth, angiogenesis and metastasis. It did not affect FGF2/heparin interaction, but inhibited FGF2 binding to immobilized receptors (IC50 ~30 μM), it disrupted FGF2 interaction with FGFR1, and had no effect on the interaction activity of growth factors with heparin or HSPGs .
Administered by injection and oral route, NSC-12 inhibits FGFR activation, tumor growth, angiogenesis and metastasis in FGF-dependent mouse and human tumor models. In animal models, it significantly reduced tumor weight, tumor cell FGFR1 phosphorylation levels and proliferation, and tumor CD31+ cardiovascular formation.
| Target | Value |
FGF3
(Cell-free assay) | 15.9 μM(Kd) |
FGF8b
(Cell-free assay) | 18.9 μM(Kd) |
FGF22
(Cell-free assay) | 26.8 μM(Kd) |
FGF20
(Cell-free assay) | 29.4 μM(Kd) |
FGF2/FGFR
(Cell-free assay) | 30 μM |
[1] Ronca R, et al. Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy. Cancer Cell. 2015 Aug 10;28(2):225-39. DOI:
10.1016/j.ccell.2015.07.002
