PD 166866

Description

PD 166866 is a potent inhibitor of fibroblast growth factor receptor 1 (FGFR1; IC₅₀ = 52.4 nM; K_i = 45.2 nM). It is selective for FGFR1 over PDGFR, EGFR, C-SRC, MEK, PKC, insulin receptor tyrosine kinase, and CDK4 (IC₅₀s = >50 μM). PD 166866 inhibits FGFR1 autophosphorylation in NIH3T3 and L6 cells (IC₅₀s = 10.8 and 3.1 nM, respectively) and inhibits phosphorylation of MAPK (IC₅₀s = 4.3 and 7.9 nM for the 44- and 42-kDa MAPK isoforms, respectively). It reduces FGF- but not EGF- or PDGF-stimulated growth of L6 cells and inhibits microvessel outgrowth from human placental arteries in vitro. PD 166866 inhibits the growth of non-small cell lung cancer (NSCLC) cell lines in a dose-dependent manner and reduces migration of VL-8 cells at a concentration of 10 μM.

Chemical properties

Off-White Solid

The Uses of PD 166866

A novel potent ATP competitive pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. An inhibitor of the basic fibroplast growth factor (bFGF).

What are the applications of Application

FGF Receptor Tyrosine Kinase Inhibitor is a cell-permeable compound that acts as an ATP-competitive inhibitor of FGFR

What are the applications of Application

PD 166866 is an inhibitor for both ATP competitive pyrido [2,3-d]pyrimidine tyrosine kinase and for bFGF

Definition

ChEBI: PD-166866 is a member of the class of pyridopyrimidines that is pyrido[2,3-d]pyrimidine substituted by an amino group at position 2, 3,5-dimethoxyphenyl group at position 6, and by a (tert-butylcarbamoyl)nitrilo group at position 7. It is a selective ATP competitive inhibitor of the human fibroblast growth factor-1 receptor (FGFR1) tyrosine kinase with an IC50 of 52.4 nM. It has a role as an apoptosis inducer, an antineoplastic agent, an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor and an angiogenesis inhibitor. It is a dimethoxybenzene, a pyridopyrimidine, a member of ureas, a biaryl and a primary arylamine.

Biochem/physiol Actions

PD-166866 is a selective inhibitor of the FGF-1 receptor tyrosine kinase (FGFR1) with IC50 = 55 nM, and no effect on c-Src, PDGFR-b, EGFR or insulin receptor tyrosine kinases or MEK, PKC, and CDK4.