PD-166866（Cat No.:R010806）is a selective inhibitor of fibroblast growth factor receptor 1 (FGFR1), a tyrosine kinase involved in cell growth, differentiation, and angiogenesis. By blocking FGFR1 signaling, PD-166866 disrupts pathways essential for tumor proliferation and vascular development, making it a valuable compound in cancer research. It has been studied for its potential to inhibit the growth of FGFR1-driven tumors and prevent angiogenesis in various cancers. PD-166866 is also used to explore the role of FGFR1 in developmental biology and disease processes, providing insights into targeted cancer therapies.
| Catalog Number | R010806 |
| CAS Number | 192705-79-6 |
| Synonyms | N-[2-Amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N’-(1,1-dimethylethyl)urea; |
| Molecular Formula | C20H24N6O3 |
| Purity | ≥95% |
| Target | FGFR inhibitor |
| Storage | -20°C |
| IUPAC Name | 1-[2-amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea |
| InChI | InChI=1S/C20H24N6O3/c1-20(2,3)26-19(27)25-17-15(8-12-10-22-18(21)24-16(12)23-17)11-6-13(28-4)9-14(7-11)29-5/h6-10H,1-5H3,(H4,21,22,23,24,25,26,27) |
| InChIKey | NHJSWORVNIOXIT-UHFFFAOYSA-N |
| SMILES | CC(C)(C)NC(=O)NC1=C(C=C2C=NC(=NC2=N1)N)C3=CC(=CC(=C3)OC)OC |
| Reference | 1:J Pharmacol Exp Ther. 1998 Jul;286(1):569-77. In vitro biological characterization and antiangiogenic effects of PD 166866, a selective inhibitor of the FGF-1 receptor tyrosine kinase.Panek RL,Lu GH,Dahring TK,Batley BL,Connolly C,Hamby JM,Brown KJ, PMID: 9655904 </br><span>Abstract:</span> Through direct synthetic efforts, we discovered a small molecule that is a nanomolar inhibitor of the human fibroblast growth factor-1 receptor (FGFR) tyrosine kinase. PD 166866, a member of a new structural class of tyrosine kinase inhibitors, the 6-aryl-pyrido[2,3-d]pyrimidines, was identified by screening a compound library with assays that measure protein tyrosine kinase activity. PD 166866 inhibited human full-length FGFR-1 tyrosine kinase with an IC50 value of 52.4 +/- 0.1 nM and was further characterized as an ATP competitive inhibitor of the FGFR-1. In contrast, PD 166866 had no effect on c-Src, platelet-derived growth factor receptor-beta, epidermal growth factor receptor or insulin receptor tyrosine kinases or on mitogen-activated protein kinase, protein kinase C and CDK4 at concentrations as high as 50 microM. PD 166866 was a potent inhibitor of basic fibroblast growth factor (bFGF)-mediated receptor autophosphorylation in NIH 3T3 cells expressing endogenous FGFR-1 and in L6 cells overexpressing the human FGFR-1 tyrosine kinase, confirming a tyrosine kinase-mediated mechanism. PD 166866 also inhibited bFGF-induced tyrosine phosphorylation of the 44- and 42-kDa (ERK 1/2) mitogen-activated protein kinase isoforms in L6 cells, presumably via inhibition of bFGF-stimulated FGFR-1 tyrosine kinase activation. PD 166866 did not inhibit platelet-derived growth factor, epidermal growth factor or insulin-stimulated receptor autophosphorylation in vascular smooth muscle, A431 or NIHIR cells, respectively, further supporting its specificity for the FGFR-1. In addition, daily exposure of PD 166866 to L6 cells at concentrations from 1 to 100 nM resulted in a concentration-related inhibition of bFGF-stimulated cell growth for 8 consecutive days with an IC50 value of 24 nM. In contrast, PD 166866 had little effect on platelet-derived growth factor-BB-stimulated growth of L6 cells or serum-stimulated vascular smooth muscle cell proliferation. Finally, PD 166866 was found to be a potent inhibitor of microvessel outgrowth (angiogenesis) from cultured artery fragments of human placenta. These results highlight the discovery of PD 166866, a new nanomolar potent and selective small molecule inhibitor of the FGFR-1 tyrosine kinase with potential use as antiproliferative/antiangiogenic agent for such therapeutic targets as tumor growth and neovascularization of atherosclerotic plaques. |
