PD-166866

Catalog No.S8493 Batch:S849304

Technical Data

Formula

C₂₀H₂₄N₆O₃

Molecular Weight

396.44

CAS No.

192705-79-6

Solubility (25°C)*

In vitro

DMSO

21 mg/mL (52.97 mM)

Ethanol

4 mg/mL (10.08 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

0.5mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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.)

Preparing Stock Solutions

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

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.