| Stereochemistry | ACHIRAL |
| Molecular Formula | C16H14BrN3O2 |
| Molecular Weight | 360.205 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC2=C(C=C1OC)C(NC3=CC(Br)=CC=C3)=NC=N2
InChI
InChIKey=LSPANGZZENHZNJ-UHFFFAOYSA-N
InChI=1S/C16H14BrN3O2/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11/h3-9H,1-2H3,(H,18,19,20)
PD-153035 is a potent and selective ATP-competitive inhibitor of the epidermal growth factor receptor tyrosine kinase EGFR. PD 153035 shows a potent and selective inhibitory effect on tyrosine phosphorylation induced by EGF in Swiss 3T3 fibroblast and A-431 human epidermoid carcinoma cells. PD153035 shows dose-dependent growth inhibitory effects in cultures of EGF receptor-overexpressing human cancer cell lines (A431, Difi, DU145, MDA-MB-468, and ME180) and in nasopharyngeal carcinoma (NPC) cell lines (NPC-TW01, NPC-TW04, and HONE1). Pretreatment of EGFR inhibitors by 24 hours significantly enhances the cytotoxic effect of doxorubicin, paclitaxel, cisplatin, and 5-fluorouracil in NPCTW04 cells. PD153035 abolishes COX-2 expression induced by the PAR(2)-activating peptide 2-furoyl-LIGRLO-NH(2) (2fLI) in Caco-2 colon cancer cells. In A431 human epidermoid tumors grown as xenografts in immunodeficient nude mice, PD153035 at 80 mg/kg i.p. inhibit EGF receptor tyrosine kinase activity. PD153035 improves glucose tolerance, insulin sensitivity, and signaling and reduces subclinical inflammation in HFD-fed mice.
CNS Activity
Originator
Approval Year
Doses
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Sourcing
PubMed
Patents
Sample Use Guides
Nude mice were treated i.p. with PD-153035 as a single dose 80 mg/kg
Route of Administration:
Intraperitoneal
A43l, MDA-MB-231, MDA-MB-453, MDA-MB-468, SK-BR-3, DU145, and Difi cells were used for activity evaluation. Cells were seeded in six well plates (model 3046; Falcon, Lincoln Park, NJ) at l0^4 cells/well. The next day, cells were changed to medium containing 0.5% FBS for 18 h, and then PD153035 (0.125, 0.25, 0.5 and 2.5 mkM) was added to the cultures. After 72 h of treatment, cells were washed once with PBS, harvested with 0.1% human trypsin-l mM EDTA in PBS, and counted with a Coulter counter.
ACTIVE MOIETY
SALT/SOLVATE (PARENT)
