PD-166866

Catalog No.S8493 Batch:S849303

Technical Data

Formula	C₂₀H₂₄N₆O₃
Molecular Weight	396.44	CAS No.	192705-79-6
Solubility (25°C)*	In vitro	DMSO	31 mg/mL (78.19 mM)
		Ethanol	8 mg/mL (20.17 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

PD-166866 is a synthetic molecule inhibiting the tyrosin kinase action of FGFR1, shows a very high selectivity towards FGFR1 and inhibits the auto-phosphorylation activity of FGRF1.

Targets

FGFR1 ^[2]
(Cell-free assay)

52.4 nM

In vitro

The treatment with PD166866 apparently causes a mitochondrial deficit and an oxidative stress^[1]. PD 166866 inhibits human full-length FGFR-1 tyrosine kinase with an IC50 value of 52.4 ± 0.1 nM but has no effect on c-Src, platelet-derived growth factor receptor-β, 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 μM. PD 166866 is 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 does 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. Besides, PD 166866 is found to be a potent inhibitor of microvessel outgrowth (angiogenesis) from cultured artery fragments of human placenta. Phosphorylated 44- and 42-kDa MAPK isoforms are inhibited in L6 cells by PD 166866 with IC50 values of 4.3 and 7.9 nM, respectively^[2]. PD166866 induces autophagy through repressing Akt/mTOR signaling pathway^[3].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines HeLa cells Concentrations 50 μM Incubation Time 24 h Method HeLa cells are treated with PD166866 for 24 hours, the growth medium is removed, the cells are washed with PBS and fixed for 1 hour at 25°C adding a freshly made paraformaldheyde solution (4% in PBS). Samples are washed again with PBS and the endogenous oxidases were blocked for 2 minutes in the dark. Further washes with PBS followed and blocking the unspecific sites is done for 1 hour at 25℃. PARP is evidenced by immunolocalization utilizing a polyclonal antibody, directed against the N-terminal proteolytic fragment. Immuno-reaction is revealed by a secondary anti-rabbit antibody after incubation for 16 hours at 4°C. After exhaustive washing with PBS the samples are incubated for 30 minutes in solution ABC. Eventually, DAB (3,3'-Diaminobenzidine) is added and the samples are incubated for 10 minutes in the dark. The samples are washed again the plates are sealed and ready for microscopic observation.
Animal Study:^{^[3]}	Animal Models Female nude mice Dosages 20 mg/kg Administration i.p.

Cell Assay:^{^[1]}

Cell lines
HeLa cells
Concentrations
50 μM
Incubation Time
24 h
Method
HeLa cells are treated with PD166866 for 24 hours, the growth medium is removed, the cells are washed with PBS and fixed for 1 hour at 25°C adding a freshly made paraformaldheyde solution (4% in PBS). Samples are washed again with PBS and the endogenous oxidases were blocked for 2 minutes in the dark. Further washes with PBS followed and blocking the unspecific sites is done for 1 hour at 25℃. PARP is evidenced by immunolocalization utilizing a polyclonal antibody, directed against the N-terminal proteolytic fragment. Immuno-reaction is revealed by a secondary anti-rabbit antibody after incubation for 16 hours at 4°C. After exhaustive washing with PBS the samples are incubated for 30 minutes in solution ABC. Eventually, DAB (3,3'-Diaminobenzidine) is added and the samples are incubated for 10 minutes in the dark. The samples are washed again the plates are sealed and ready for microscopic observation.

Animal Study:^{^[3]}

Animal Models
Female nude mice
Dosages
20 mg/kg
Administration
i.p.

References

Selleck's PD-166866 has been cited by 12 publications

Paradoxical cancer cell proliferation after FGFR inhibition through decreased p21 signaling in FGFR1-amplified breast cancer cells [ Breast Cancer Res, 2024, 26(1):54]	PubMed: 38553760
Crosstalk of growth factor receptors at plasma membrane clathrin-coated sites [ bioRxiv, 2024, 2024.05.16.594559]	PubMed: 38903101
Targeting FAPα-expressing hepatic stellate cells overcomes resistance to anti-angiogenics in colorectal cancer liver metastasis models [ J Clin Invest, 2022, e157399]	PubMed: 35951441
FGF8-FGFR1 signaling regulates human GnRH neuron differentiation in a time- and dose-dependent manner [ Dis Model Mech, 2022, 15(8)dmm049436]	PubMed: 35833364
Regulation of STUB1 expression and its biological significance in mouse Sertoli cells [ Syst Biol Reprod Med, 2022, 1-15]	PubMed: 35343345
Probing the signaling requirements for naive human pluripotency by high-throughput chemical screening [ Cell Rep, 2021, 35(11):109233]	PubMed: 34133938
The Roles of FGF21 and ALCAT1 in Aerobic Exercise-Induced Cardioprotection of Postmyocardial Infarction Mice [ Oxid Med Cell Longev, 2021, 2021:8996482]	PubMed: 34777697
Activation of Serum/Glucocorticoid Regulated Kinase 1/Nuclear Factor-κB Pathway Are Correlated with Low Sensitivity to Bortezomib and Ixazomib in Resistant Multiple Myeloma Cells [ Biomedicines, 2021, 9(1)E33]	PubMed: 33406639
Identification of testicular Foxq1 as a critical modulator of lactate metabolism in mouse Sertoli cells [ Histochem Cell Biol, 2021, 156(3):227-237]	PubMed: 34091745
Rab8 and Rabin8-Mediated Tumor Formation by Hyperactivated EGFR Signaling via FGFR Signaling [ Int J Mol Sci, 2020, 21(20)E7770]	PubMed: 33092268

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