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Purity: ≥98%
PD168393 (PD-168393) is covalent / irreversible, cell-permeable and ATP-competitive EGFR inhibitor with potential anticancer activity. With an IC50 of 0.70 nM, it inhibits EGFR. With no effect on insulin, PDGFR, FGFR, or PKC, PD 168393 functions by permanently alkylating the Cys-773 residue of EGFR.
| Targets |
EGFR (IC50 = 0.7 nM)
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| ln Vitro |
PD 168393 docks into EGFR TK's ATP binding pocket. In A431 cells, continuous exposure to PD168393 completely stops EGF-dependent receptor autophosphorylation, and the suppression continues even after 8 hours in compound-free medium. With an IC50 of 5.7 nM, PD168393 prevents heregulin-induced tyrosine phosphorylation in MDA-MB-453 cells. PD168393 is not active against PKC, insulin, PDGF, or basic FGFR TKs. With an IC50 of 1-6 nM, PD168393 suppresses EGF-mediated tyrosine phosphorylation in HS-27 human fibroblasts but has no effect on PDGF- or FGF-mediated tyrosine phosphorylation.[1] In 3T3-Her2 cells, PD168393 exhibits a swift and strong suppression of Her2-induced tyrosine phosphorylation, with an IC50 of approximately 100 nM. In 3T3-Her2 cells, D168393 also prevents PLCγ1/Stat1/Dok1/δ-catenin from being phosphorylated, with the exception of Fyb.[2]
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| ln Vivo |
PD168393 (intraperitoneal injection; 58 mg/kg; once daily; days 10-14, 17-21, and 24-28) is efficacious in vivo, exhibiting 115% tumor growth inhibition in human epidermoid carcinoma xenografts in mice following a 15-day treatment period.
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| Enzyme Assay |
PD168393 is an potent, cell-permeable, irreversible EGFR inhibitor that irreversibly alkylates Cys-773. It is inactive against PDGFR, FGFR, PKC, and insulin. Its IC50 is 0.70 nM. goal: EGFR IC 50 = 0.7 nM (1) PD 168393 has >9-fold higher potency than PD 174265 in inhibiting EGFr autophosphorylation in A431 human epidermoid carcinoma cells. (2) In cardiomyocytes stimulated by lipopolysaccharide (LPS), PD 168393 reduces TNF-α production and phosphorylation of ERK1/2 and p38. (3) At concentrations as low as 0.03 umol/L, PD168393 totally inhibits the phosphorylation of AKT and ERK. (4) In ErbB2 positive lung and breast cancer cell lines, PD168393 may cause apoptosis and suppress cell growth. (5) The inhibition of phospho-p44/42 ERK indicated that PD168393 interfered with MEK1/p44/42 ERK signaling in HaCaT cells.
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| Cell Assay |
(1) PD 168393 has >9-fold higher potency than PD 174265 in inhibiting EGFr autophosphorylation in A431 human epidermoid carcinoma cells. (2) In cardiomyocytes stimulated by lipopolysaccharide (LPS), PD 168393 reduces TNF-α production and phosphorylation of ERK1/2 and p38. (3) At concentrations as low as 0.03 umol/L, PD168393 totally inhibits the phosphorylation of AKT and ERK. (4) In ErbB2 positive lung and breast cancer cell lines, PD168393 may cause apoptosis and suppress cell growth.
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| Animal Protocol |
Athymic nude mice with A431 human epidermoid carcinoma
58 mg/kg i.p. |
| References |
| Molecular Formula |
C17H13BRN4O
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| Molecular Weight |
369.22
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| Exact Mass |
368.03
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| Elemental Analysis |
C, 55.30; H, 3.55; Br, 21.64; N, 15.17; O, 4.33
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| CAS # |
194423-15-9
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| Appearance |
Solid powder
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| SMILES |
C=CC(=O)NC1=CC2=C(C=C1)N=CN=C2NC3=CC(=CC=C3)Br
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| InChi Key |
HTUBKQUPEREOGA-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
N-[4-(3-bromoanilino)quinazolin-6-yl]prop-2-enamide
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| Synonyms |
PD 168393; PD-168393; PD168393
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 30% PEG400+0.5% Tween80+5% propylene glycol: 30mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7084 mL | 13.5421 mL | 27.0841 mL | |
| 5 mM | 0.5417 mL | 2.7084 mL | 5.4168 mL | |
| 10 mM | 0.2708 mL | 1.3542 mL | 2.7084 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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. |
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