PD158780 - EGFR 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPD158780Cat. No.: HY-18609CAS No.: 171179-06-9分式: CHBrN分量: 330.18作靶點(diǎn): EGFR作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 21 mg/mL (63.60

2、 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 3.0287 mL 15.1433 mL 30.2865 mL5 mM 0.6057 mL 3.0287 mL 6.0573 mL10 mM 0.3029 mL 1.5143 mL 3.0287 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 PD158780是有效地 EGFR 家族抑制劑；對(duì)EGFR，ErbB2，ErbB3和ErbB4的

3、IC50 值分別為8 M，49，52，52 nM。IC50 & Target EGFR ErbB2 ErbB3 ErbB48 M (IC50, Cell Assay) 49 nM (IC50, Cell 52 nM (IC50, Cell 52 nM (IC50, CellAssay) Assay) Assay)1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 PD158780 inhibits EGF receptor autophosphorylation in A431 human epidermoid carcinoma wit

4、h IC50 valueof 13 nM. PD158780 is highly specific for the EGF receptor in Swiss 3T3 fibroblasts, inhibiting EGF-dependent receptor autophosphorylation and thymidine incorporation at low nanomolar concentrations whilerequiring micromolar levels for platelet-derived growth factor- and basic fibroblast

5、 growth factordependentprocesses. PD158780 inhibits heregulin-stimulated phosphorylation in the SK-BR-3 and MDAMB-453 breastcarcinomas with IC50 values of 49 and 52 nM, respectively, suggesting that the compound is active againstother members of the EGF receptor family 1.體內(nèi)研究 PD158780 is active agai

6、nst clone formation in several breast tumors having different expression patterns ofthe ErbB family. PD158780 shows good therapeutic effect against the A431 epidermoid carcinoma whenadministered either intraperitoneally or orally. PD158780 produces measurable, significant effects against amouse fibr

7、oblast transfected with human EGFR. PD158780 produces a significant therapeutic effect againstthe estrogendependent MCF-7 breast carcinoma at equitoxic dose levels 1.PROTOCOLKinase Assay 1 The enzyme assay is performed in 96-well filter plates. The total volume is 0.1 mL containing 20 mM HEPES,pH 7.

8、4, 50 M sodium vanadate, 40 mM magnesium chloride, 10 M ATP containing 0.5 Ci of 32pATP, 20g of polyglutamic acid/tyrosine, 1 ng of EGF receptor tyrosine kinase, ard appropriate dilutions of inhibitor(PD158780) and/or ATP. All corrtponents except the ATP are added to the well, and the plate is incub

9、atedwith shaking for 10 min at 25C. The reaction is started by adding 32pATP, and the plate is incubated withshaking at 25C for 10 min. The reaction is terminated by the addition of 0.1 mL of 20% TCA, and the plate iskept at 4C for at least 15 min to allow the substrate to precipitate. The wells are

10、 then ished five times with0.125 mL of 10% TCA, and 32p incorporation is determined 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 All cell lines are maintained as monolayers in dMEM/F12, 50:50 containing 10% fetal bovine serum. Forgrowt

11、h inhibition assays, dilutions of the designated compound (PD158780) in 10 L are placed in 24-wellplates followed by the addition of cells in 2 mL of medium. The plates are incubated for 72 hr at 37C in ahumidified atmosphere. Cell growth is determined by counting cells 1.MCE has not independently c

12、onfirmed the accuracy of these methods. They are for reference only.Animal Tumor fragments were implanted sc into the right axilla of mice on day 0. PD158780 is administeredAdministration 1 intraperitoneally or orally. Tumor growth is monitored 1.MCE has not independently confirmed the accuracy of t

13、hese methods. They are for reference only.REFERENCES1. Fry DW, et al. Biochemical and antiproliferative properties of 4-ar(alk)ylaminopyridopyrimidines, a new chemical class of potent andspecific epidermal growth factor receptor tyrosine kinase inhibitor. Biochem Pharmacol. 1997 Oct 15;54(8):877-87.McePdfH