PD153035 HCl

 

 

 

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	PD153035 is a potent and specific inhibitor of EGFR with Ki and IC50 of 5.2 pM and 29 pM; little effect noted against PGDFR, FGFR, CSF-1, InsR and Src.
Targets	EGFR	EGFR
IC50	5.2 pM (Ki)	29 pM [1]
In vitro	PD 153035 shows a potent and selective inhibitory effect on tyrosine phosphorylation induced with EGF with IC50 of 15 nM and 14 nM in Swiss 3T3 fibroblast and A-431 human epidermoid carcinoma cells, respectively.[1] PD153035 shows growth inhibitory effects in cultures of EGF receptor-overexpressing human cancer cell lines including A431, Difi, DU145, MDA-MB-468 and ME180 cells with IC50 of 0.22 μM, 0.3μM, 0.4 μM, 0.68 μM and 0.95 μM, respectively. [2] PD153035 induces a dose-dependent growth inhibition in nasopharyngeal carcinoma (NPC) cells including NPC-TW01, NPC-TW04, and HONE1 cell lines with IC50 of 12.9 μM, 9.8 μM and 18.6μM, respectively. [3] A recent study shows that PD153035 abolishes COX-2 expression induced by the PAR(2)-activating peptide 2-furoyl-LIGRLO-NH(2) (2fLI) in Caco-2 colon cancer cells. [4]
In vivo	In A431 human epidermoid tumors grown as xenografts in immunodeficient nude mice, PD153035 at 80 mg/kg inhibit EGF receptor tyrosine kinase activity. [5] PD153035 improves glucose tolerance, insulin sensitivity, and signaling and reduces subclinical inflammation in HFD-fed mice. [6] Pretreatment of EGFR inhibitors by 24 hours significantly enhances the cytotoxic effect of doxorubicin, paclitaxel, cisplatin, and 5-fluororuacil in NPCTW04 cells. [3]
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

Inhibition of EGF receptor tyrosine kinase

Enzyme reactions are performed in a total volume of 0.1 mL containing 25 mM Hepes (pH 7.4), 5 mM MgCl2, 2 mM MnCl2, 50 μM sodium vanadate, 0.5 to 1.0 ng of enzyme (which also contains enough EGF to make the final concentrations 2 μg/mL), 10 μM ATP containing 1 μCi of [32P]ATP, varying concentrations of PD153035, and 200 μM of a substrate peptide based on a portion of phospholipase C-γl having the sequence Lys-His-Lys-Lys-Leu-Ala-Glu-Gly-Ser-Ala-Tyr472-Glu-Glu-Val. The reaction is initiated by the addition of ATP. After 10 minutes at room temperature, the reaction is terminated by addition of 2 mL of 75 mM phosphoric acid, and the solution is passed through a 2.5-cm phosphocellulose filter disk that binds the peptide. The filter is washed five times with 75 mM phosphoric acid and placed in a vial with 5 mL of scintillation fluid. The uninhibited control activity produces approximately 100,000 cpm.

Cell Assay: ^[2]

Cell lines	A431, Difi, DU145, MDA-MB-468 and ME180
Concentrations	0-3 μM
Incubation Time	72 hours
Method	Cells are seeded in sixwell plates. The next day, cells are changed to medium containing 0.5% FBS for 18 hours, and then PD153035 is added at various concentrations to the cultures. After 72 hours of treatment, cells are washed once with PBS, harvested with 0.1% human trypsin-l mM EDTA in PBS, and counted with a Coulter counter. The CMK cells grow in suspension and, therefore, do not require trypsinization.

Animal Study: ^[5]

Animal Models	A431 cells are injected into the outbred nude mice.
Dosages	≤80 mg/kg
Administration	Administered via i.p.
Solubility	30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL

1

References

Chemical Information

Download PD153035 HCl SDF

Chemical Name	N-(3-bromophenyl)-6,7-dimethoxyquinazolin-4-amine hydrochloride

Customer Reviews (2)

Click to enlarge	Rating
	Source	J Immunol, 2012, 188(9), 4581-4589 . PD153035 HCl purchased from Selleck
	Method	Western blot
	Cell Lines	RCH-ACV cell
	Concentrations	1 μM
	Incubation Time
	Results	Pretreatment with EGFR kinase inhibitors, PD153035 and EKB-569, a potent irreversible inhibitor, abolished the IGF-1- and IL-1β-mediated increase in Bcl-2mRNA levels.

Product Citations (1)

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  Inhibition of poxvirus spreading by the anti-tumor drug Gefitinib (Iressa™). [Langhammer S, et al. Antivir Res 2010;89(1):64-70]

  
  PubMed: 21094187