PD-166866

製品コードS8493 バッチS849302

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₀H₂₄N₆O₃
	分子量	396.44	CAS No.	192705-79-6
Solubility (25°C)*	体外	DMSO	40 mg/mL warmed with 50ºC water bath (100.89 mM)
		Ethanol	4 mg/mL warmed with 50ºC water bath (10.08 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.

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生物活性

製品説明	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.
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].

製品説明

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.

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].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	HeLa cells
	濃度	50 μM
	反応時間	24 h
	実験の流れ	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.
動物実験	動物モデル	Female nude mice
	投薬量	20 mg/kg
	投与方法	i.p.

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
Effect of fibroblast growth factor 2 on degenerative endplate chondrocyte: From anabolism to catabolism [ Exp Mol Pathol, 2020, S0014-4800(20)30867-4]	PubMed: 33285208
Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay. [ Sci Rep, 2019, 9(1):10278]	PubMed: 31311976

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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