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Description: PD168393 (PD-168393) is covalent / irreversible, cell-permeable and ATP-competitive EGFR inhibitor with potential anticancer activity. It inhibits EGFR with an IC50 of 0.70 nM. PD 168393 acts by irreversibly alkylating the Cys-773 residue of EGFR and shows no activity against insulin, PDGFR, FGFR and PKC.
References: Proc Natl Acad Sci U S A. 1998; 95: 12022–12027; Proc Natl Acad Sci U S A. 2006;103:9773-8.
InChi Key: HTUBKQUPEREOGA-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H13BrN4O/c1-2-16(23)21-13-6-7-15-14(9-13)17(20-10-19-15)22-12-5-3-4-11(18)8-12/h2-10H,1H2,(H,21,23)(H,19,20,22)
SMILES Code: C=CC(NC1=CC2=C(NC3=CC=CC(Br)=C3)N=CN=C2C=C1)=O
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
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: PD168393 is an potent, cell-permeable, irreversible EGFR inhibitor with IC50 of 0.70 nM, irreversibly alkylate Cys-773, inactive against insulin, PDGFR, FGFR and PKC. target: EGFR IC 50: 0.7 nM (1) PD 168393 inhibite EGFr autophosphorylation in A431 human epidermoid carcinoma cells with >9-fold greater potency than PD 174265. (2) PD 168393 decrease the production of TNF-α and phosphrylation of ERK1/2 and p38 induced by LPS in cardiomyocytes. (3) PD168393 completely inhibits AKT and ERK phosphorylation at concentrations as low as 0.03 umol/L. (4) PD168393 could induce apoptosis and inhibit cell growth in ErbB2 positive lung and breast cancer cell lines. (5) PD168393 disrupted MEK1/p44/42 ERK signaling in HaCaT cells as determined by inhibition of phospho-p44/42 ERK.
Cell Assay: (1) PD 168393 inhibite EGFr autophosphorylation in A431 human epidermoid carcinoma cells with >9-fold greater potency than PD 174265. (2) PD 168393 decrease the production of TNF-α and phosphrylation of ERK1/2 and p38 induced by LPS in cardiomyocytes. (3) PD168393 completely inhibits AKT and ERK phosphorylation at concentrations as low as 0.03 umol/L. (4) PD168393 could induce apoptosis and inhibit cell growth in ErbB2 positive lung and breast cancer cell lines.
Lot#: V054701,Purity ≥98%
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The irreversible inhibitor PD168393 overcomes lapatinib resistance caused by the ErbB2 T798I mutation. PLoS One. 2014 Sep 19;9(9):e106349.
Antitumor effects of lapatinib and PD168393 in the ErbB2 positive lung cancer cell line, Calu3 and the ErbB2 positive breast cancer cell line, SkBr3 after 72 hour treatment. PLoS One. 2014 Sep 19;9(9):e106349.
Clonogenic survival assay shows that PHLDA1 overexpression could significantly enhance lapatinib sensitivity in breast cancer cells. PLoS One. 2014 Sep 19;9(9):e106349.