product name PD168393
Description: PD168393 is potent, cell-permeable, irreversible, ATP-competitive and selective EGFR inhibitor with IC50 of 0.70 nM, it irreversibly alkylates Cys-773 and is inactive against insulin, PDGFR, FGFR and PKC. PD168393 has a high specificity toward the EGFR with Cys-773 which inhibit the EGFR tyrosine kinase, which is on the cytoplasmic side of the receptor. Without kinase activity, EGFR is unable to activate itself, which is a prerequisite for binding of downstream adaptor proteins. Ostensibly by halting the signaling cascade in cells that rely on this pathway for growth, tumor proliferation and migration is diminished.
References: Proc Natl Acad Sci U S A. 1998; 95: 12022–12027; Proc Natl Acad Sci U S A. 2006;103:9773-8.
369.22
Formula
C17H13BrN4O
CAS No.
194423-15-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 74 mg/mL (200.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% PEG400+0.5% Tween80+5% propylene glycol: 30mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19416753
| In Vitro |
In vitro activity: PD 168393 is docked into the ATP binding pocket of EGFR TK. PD168393 completely suppresses EGF-dependent receptor autophosphorylation in A431 cells during continuous exposure, with continous suppression even after 8 hr in compound-free medium. PD168393 inhibits heregulin-induced tyrosine phosphorylation in MDA-MB-453 cells with IC50 of 5.7 nM. PD168393 is inactive against insulin, PDGF and basic FGFR TKs as well as PKC. PD168393 inhibits EGF-mediated tyrosine phosphorylation in HS-27 human fibroblasts with IC50 of 1-6 nM but has little effect on FGF- or PDGF-mediated tyrosine phosphorylation. PD168393 shows rapid and potent inhibition of Her2-induced tyrosine phosphorylation with IC50 of ~100 nM in 3T3-Her2 cells. D168393 also inhibits phosphorylation of PLCγ1/Stat1/Dok1/δ-catenin in 3T3-Her2 cells, except for Fyb. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | PD 168393 produces tumor growth inhibition of 115% in A431 human epidermoid carcinoma xenograft in nude mice, with 50% reduced phosphotyrosine content of EGFR. PD 168393 also shows a low plasma concentration. |
| Animal model | Athymic nude mice with A431 human epidermoid carcinoma |
| Formulation & Dosage | Formulated in 4% dimethylacetamide in aqueous 50 mM sodium lactate buffer (pH 4); 58 mg/kg; i.p. |
| References | Proc Natl Acad Sci U S A. 1998 Sep 29; 95(20): 12022–12027; Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9773-8. |
