CAS NO: | 194423-15-9 |
规格: | ≥98% |
包装 | 价格(元) |
1mg | 电议 |
2mg | 电议 |
5mg | 电议 |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
Molecular Weight (MW) | 369.22 |
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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 | PD 168393; PD-168393; PD168393; 4-[(3-Bromophenyl)amino]-6-acrylamidoquinazoline 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 |
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: 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. |
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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. |