product name PD153035 HCl
Description: PD153035 HCl is a potent and specific inhibitor of EGFR with Ki and IC50 of 5.2 pM and 29 pM in cell-free assays; little effect noted against PGDFR, FGFR, CSF-1, InsR and Src. PD153035 inhibits EGF-dependent EGFR phosphorylation in a variety of human cancer cell lines over-expressing EGFRs, which include A431, Difi, DU145, MDA-MB-468, ME180 and C4i, with IC50 of 0.22 μM, 0.3 μM, 0.4 μM, 0.68 μM, 0.95 μM and 2.5 μM respectively.
References: Science. 1994 Aug 19;265(5175):1093-5; Invest New Drugs. 1996;13(4):295-302.
396.67
Formula
C16H14BrN3O2.HCl
CAS No.
183322-45-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 0.5 mg/mL (1.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL
Synonyms
SU-5271 (AG1517) HCl ,ZM 252868 HCl
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19417063
| In Vitro |
In vitro activity: 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. 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. 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. 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. Kinase Assay: 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: Cells (A431, Difi, DU145, MDA-MB-468 and ME180) 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. |
|---|---|
| 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. PD153035 improves glucose tolerance, insulin sensitivity, and signaling and reduces subclinical inflammation in HFD-fed mice. Pretreatment of EGFR inhibitors by 24 hours significantly enhances the cytotoxic effect of doxorubicin, paclitaxel, cisplatin, and 5-fluororuacil in NPCTW04 cells. |
| Animal model | A431 cells are injected into the outbred nude mice. |
| Formulation & Dosage | Dissolved in water.; 80 mg/kg; i.p. injection |
| References | Science. 1994 Aug 19;265(5175):1093-5; Invest New Drugs. 1996;13(4):295-302. |
